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The orbitofrontal cortex (OFC) is crucial for tracking various aspects of expected outcomes, thereby helping to guide choices and support learning. Our previous study showed that the effects of reward timing and size on the activity of single units in OFC were dissociable when these attributes were manipulated independently (Roesch et al., 2006). However, in real-life decision-making scenarios, outcome features often change simultaneously, so here we investigated how OFC neurons in male rats integrate information about the timing and identity (flavor) of reward and respond to changes in these features, according to whether they were changed simultaneously or separately. We found that a substantial number of OFC neurons fired differentially to immediate versus delayed reward and to the different reward flavors. However, contrary to the previous study, selectivity for timing was strongly correlated with selectivity for identity. Taken together with the previous research, these results suggest that when reward features are correlated, OFC tends to “pack” them into unitary constructs, whereas when they are independent, OFC tends to “crack” them into separate constructs. Furthermore, we found that when both reward timing and flavor were changed, reward-responsive OFC neurons showed unique activity patterns preceding and during the omission of an expected reward. Interestingly, this OFC activity is similar and slightly preceded the ventral tegmental area dopamine (VTA DA) activity observed in a previous study (Takahashi et al., 2023), consistent with the role of OFC in providing predictive information to VTA DA neurons. [ABSTRACT FROM AUTHOR]

Pavlovian fear conditioning research suggests that the interaction between the dorsal periaqueductal gray (dPAG) and basolateral amygdala (BLA) acts as a prediction error mechanism in the formation of associative fear memories. However, their roles in responding to naturalistic predatory threats, characterized by less explicit cues and the absence of reiterative trial-and-error learning events, remain unexplored. In this study, we conducted single-unit recordings in rats during an ‘approach food-avoid predator’ task, focusing on the responsiveness of dPAG and BLA neurons to a rapidly approaching robot predator. Optogenetic stimulation of the dPAG triggered fleeing behaviors and increased BLA activity in naive rats. Notably, BLA neurons activated by dPAG stimulation displayed immediate responses to the robot, demonstrating heightened synchronous activity compared to BLA neurons that did not respond to dPAG stimulation. Additionally, the use of anterograde and retrograde tracer injections into the dPAG and BLA, respectively, coupled with c-Fos activation in response to predatory threats, indicates that the midline thalamus may play an intermediary role in innate antipredatory-defensive functioning.

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.

Simultaneous recordings from large populations of individual neurons across distributed brain regions over months to years will enable new avenues of scientific and clinical development. The use of flexible polymer electrode arrays can support long-lasting recording, but the same mechanical properties that allow for longevity of recording make multiple insertions and integration into a chronic implant a challenge. Here is a methodology by which multiple polymer electrode arrays can be targeted to a relatively spatially unconstrained set of brain areas. The method utilizes thin-film polymer devices, selected for their biocompatibility and capability to achieve long-term and stable electrophysiologic recording interfaces. The resultant implant allows accurate and flexible targeting of anatomically distant regions, physical stability for months, and robustness to electrical noise. The methodology supports up to sixteen serially inserted devices across eight different anatomic targets. As previously demonstrated, the methodology is capable of recording from 1024 channels. Of these, the 512 channels in this demonstration used for single neuron recording yielded 375 single units distributed across six recording sites. Importantly, this method also can record single units for at least 160 days. This implantation strategy, including temporarily bracing each device with a retractable silicon insertion shuttle, involves tethering of devices at their target depths to a skull-adhered plastic base piece that is custom-designed for each set of recording targets, and stabilization/protection of the devices within a silicone-filled, custom-designed plastic case. Also covered is the preparation of devices for implantation, and design principles that should guide adaptation to different combinations of brain areas or array designs.

The ventral hippocampus (vH) plays a crucial role in anxiety-related behaviour and vH neurons increase their firing when animals explore anxiogenic environments. However, if and how such neuronal activity induces or restricts the exploration of an anxiogenic location remains unexplained. Here, we developed a novel behavioural paradigm to motivate rats to explore an anxiogenic area. Male rats ran along an elevated linear maze with protective sidewalls, which were subsequently removed in parts of the track to introduce an anxiogenic location. We recorded neuronal action potentials during task performance and found that vH neurons exhibited remapping of activity, overrepresenting anxiogenic locations. Direction-dependent firing was homogenised by the anxiogenic experience. We further showed that the activity of vH neurons predicted the extent of exploration of the anxiogenic location. Our data suggest that anxiety-related firing does not solely depend on the exploration of anxiogenic environments, but also on intentions to explore them.

We are able to temporally organize multiple movements in a purposeful manner in everyday life. Both the dorsal premotor (PMd) area and pre-supplementary motor area (pre-SMA) are known to be involved in the performance of motor sequences. However, it is unclear how each area differentially contributes to controlling multiple motor sequences. To address this issue, we recorded singleunit activity in both areas while monkeys (one male, one female) performed sixteen motor sequences. Each sequence comprised either a series of two identical movements (repetition) or two different movements (nonrepetition). The sequence was initially instructed with visual signals but had to be remembered thereafter. Here, we showed that the activity of single neurons in both areas transitioned from reactive-to predictive encoding while motor sequences were memorized. In the memory-guided trials, in particular, the activity of PMd cells preferentially represented the second movement (2M) in the sequence leading to a reward generally regardless of the first movement (1M). Such activity frequently began even before the 1M in a prospective manner, and was enhanced in nonrepetition sequences. Behaviorally, a lack of the activity enhancement often resulted in premature execution of the 2M. In contrast, cells in pre-SMA instantiated particular sequences of actions by coordinating switching or nonswitching movements in sequence. Our findings suggest that PMd and pre-SMA play complementary roles within behavioral contexts: PMd preferentially controls the movement that leads to a reward rather than the sequence per se, whereas pre-SMA coordinates all elements in a sequence by integrating temporal orders of multiple movements. [ABSTRACT FROM AUTHOR]

Background and Objectives: Single-unit transfusions continue to be a widespread transfusion practice. Single-unit red blood cell (RBC) transfusions were treated with substantial denunciation in the past but recently have been reviewed as to whether it is acceptable or could be acceptable. This study was undertaken to observe the overall profile of the patients receiving the single-unit transfusion and analyze the possible rationale of such transfusion. Methods: This was a retrospective record-based study conducted in multispecialty tertiary level care teaching hospital over a period of 1 year from January to December 2017. Variables included were age, gender, diagnosis, indication for transfusion, pre- and post-hemoglobin, additional modality of treatment received including other blood components and length of hospital stay. Qualitative variables were described as number and percentages, and quantitative variables as number, mean, and standard deviation. Results: During the study, 50,880 blood components were issued out of which, packed RBCs (PRBCs) accounted to 19760. Twenty-four percent (4742 units) of the total blood units were transfused as single unit of PRBC. 52.1% of these single-unit transfusions were carried out by the surgical specialties. Conclusion: Single-unit transfusions are more common in medical specialties probably due to the chronic nature of the diseases. However, even in surgical specialties, especially those striving toward reducing blood usage and the ones operating in more of an elective setting, single-unit transfusions were higher.

The amygdala is a highly connected cluster of nuclei with input from multiple sensory modalities, particularly the ventral visual stream, and vast projections to distributed cortical and subcortical regions involved in autonomic regulation and cognition. 1-4 Numerous studies have described the amygdala's capacity to facilitate the encoding of long-lasting emotional memories. 5-15 Recently, direct electrical stimulation of the basolateral complex of the amygdala (BLA) in humans revealed a more generalized ability to enhance declarative memory irrespective of the emotional valence 16 , likely by promoting synaptic plasticity-related processes underlying memory consolidation in the hippocampus and medial temporal lobe. 17-20 These effects were achieved with rhythmic theta-burst stimulation (TBS), which is known to induce long-term potentiation (LTP), a key mechanism in memory formation. 21 Emerging evidence suggests that intracranial TBS may also enhance memory specificity 22 , evoke theta-frequency oscillations 23 , and facilitate short-term plasticity in local field potential recordings. 24,25 However, how amygdalar TBS modulates activity at the single-cell level and to what extent this modulation is associated with memory performance remain poorly understood. Here, we address this knowledge gap by conducting simultaneous microelectrode recordings from prefrontal and medial temporal structures during a memory task in which intracranial TBS was applied to the BLA. We observed a subset of neurons whose firing rate was modulated by TBS and exhibited highly heterogeneous responses with respect to onset latency, duration, and direction of effect. Notably, location and baseline activity predicted which neurons were most susceptible to modulation. These findings provide direct empirical support for stimulation-evoked modulation of single-neuron activity in humans, which has implications for the development and refinement of neuromodulatory therapies., Competing Interests: Competing Interests None.

Single-unit (SU) activity-action potentials isolated from one neuron-has traditionally been employed to relate neuronal activity to behavior. However, recent investigations have shown that multiunit (MU) activity-ensemble neural activity recorded within the vicinity of one microelectrode-may also contain accurate estimations of task-related neural population dynamics. Here, using an established model-fitting approach, we compared the spatial codes of SU response fields with corresponding MU response fields recorded from the frontal eye fields (FEFs) in head-unrestrained monkeys ( Macaca mulatta ) during a memory-guided saccade task. Overall, both SU and MU populations showed a simple visuomotor transformation: the visual response coded target-in-eye coordinates, transitioning progressively during the delay toward a future gaze-in-eye code in the saccade motor response. However, the SU population showed additional secondary codes, including a predictive gaze code in the visual response and retention of a target code in the motor response. Further, when SUs were separated into regular/fast spiking neurons, these cell types showed different spatial code progressions during the late delay period, only converging toward gaze coding during the final saccade motor response. Finally, reconstructing MU populations (by summing SU data within the same sites) failed to replicate either the SU or MU pattern. These results confirm the theoretical and practical potential of MU activity recordings as a biomarker for fundamental sensorimotor transformations (e.g., target-to-gaze coding in the oculomotor system), while also highlighting the importance of SU activity for coding more subtle (e.g., predictive/memory) aspects of sensorimotor behavior., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Seo et al.)

Background and Objectives: Single-unit transfusions continue to be a widespread transfusion practice. Single-unit red blood cell (RBC) transfusions were treated with substantial denunciation in the past but recently have been reviewed as to whether it is acceptable or could be acceptable. This study was undertaken to observe the overall profile of the patients receiving the single-unit transfusion and analyze the possible rationale of such transfusion. Methods: This was a retrospective record-based study conducted in multispecialty tertiary level care teaching hospital over a period of 1 year from January to December 2017. Variables included were age, gender, diagnosis, indication for transfusion, pre- and post-hemoglobin, additional modality of treatment received including other blood components and length of hospital stay. Qualitative variables were described as number and percentages, and quantitative variables as number, mean, and standard deviation. Results: During the study, 50,880 blood components were issued out of which, packed RBCs (PRBCs) accounted to 19760. Twenty-four percent (4742 units) of the total blood units were transfused as single unit of PRBC. 52.1% of these single-unit transfusions were carried out by the surgical specialties. Conclusion: Single-unit transfusions are more common in medical specialties probably due to the chronic nature of the diseases. However, even in surgical specialties, especially those striving toward reducing blood usage and the ones operating in more of an elective setting, single-unit transfusions were higher. [ABSTRACT FROM AUTHOR]

A fundamental feature of sleep is reduced behavioral responsiveness to external events, but the extent of processing along sensory pathways remains poorly understood. While responses are comparable across wakefulness and sleep in auditory cortex (AC), neuronal activity in downstream regions remains unknown. Here we recorded spiking activity in 435 neuronal clusters evoked by acoustic stimuli in the perirhinal cortex (PRC) and in AC of freely behaving male rats across wakefulness and sleep. Neuronal responses in AC showed modest (~ 10%) differences in response gain across vigilance states, replicating previous studies. By contrast, PRC neuronal responses were robustly attenuated by 47% and 36% during NREM sleep and REM sleep, respectively. Beyond the separation according to cortical region, response latency in each neuronal cluster was correlated with the degree of NREM sleep attenuation, such that late (>40 ms) responses in all monitored regions diminished during NREM sleep. The robust attenuation of late responses prevalent in PRC represents a novel neural correlate of sensory disconnection during sleep, opening new avenues for investigating the mediating mechanisms. [ABSTRACT FROM AUTHOR]

Faced with potential harm, individuals must estimate the probability of threat and initiate an appropriate fear response. In the prevailing view, threat probability estimates are relayed to the ventrolateral periaqueductal gray (vlPAG) to organize fear output. A straightforward prediction is that vlPAG single-unit activity reflects fear output, invariant of threat probability. We recorded vlPAG single-unit activity in male, Long Evans rats undergoing fear discrimination. Three 10 s auditory cues predicted unique foot shock probabilities: danger (p=1.00), uncertainty (p=0.375) and safety (p=0.00). Fear output was measured by suppression of reward seeking over the entire cue and in one-second cue intervals. Cued fear non-linearly scaled to threat probability and cue-responsive vlPAG single-units scaled their firing on one of two timescales: at onset or ramping toward shock delivery. VlPAG onset activity reflected threat probability, invariant of fear output, while ramping activity reflected both signals with threat probability prioritized.

• We conducted a phase 2 single-arm prospective study of cord blood transplantation (CBT). • We assessed the efficacy of CBT for treating patients with adult acute leukemia and myelodysplastic syndrome. • CBT showed significantly better day 180 overall survival than threshold survival. • CBT outcomes are comparable to historical unrelated donor transplantation in adults with low comorbidity. • Patients with high-risk features in complete response status may benefit from early CBT. Almost comparable transplantation outcomes have been reported with HLA-matched unrelated donor transplantation (UDT) and cord blood transplantation (CBT). We conducted a prospective phase 2 study to assess the efficacy and safety of single-unit myeloablative CBT in adult leukemia and myelodysplastic syndrome. Because the day 180 survival of UDT was approximately 80%, we determined the alternative hypothesis of expected day 180 survival with a successful engraftment rate of 80% and set the null hypothesis of threshold rate at 65%. Sixty-two patients (median age, 37 years) were registered, including 28 with acute myelogenous leukemia, 25 with acute lymphoblastic leukemia, and 9 with myelodysplastic syndrome. Of 61 eligible patients, 52 were successfully engrafted and survived at day 180 (85%; 95% confidence interval, 74% to 93%). Single-unit CBT was judged to be effective because the null hypothesis was rejected (P <.001). Furthermore, neutrophil engraftment was observed in 57 patients (92%); the incidences of grade II-IV acute and chronic graft-versus-host disease were 30% and 32%, respectively; and the cumulative incidences of nonrelapse mortality and relapse at 2 years were 18% and 13%, respectively. The present study showed favorable survival outcomes with single-unit CBT. Therefore, this method may be considered if a well-HLA-matched UDT cannot be obtained. [ABSTRACT FROM AUTHOR]

Natural sounds such as vocalizations often have covarying acoustic attributes, resulting in redundancy in neural coding. The efficient coding hypothesis proposes that sensory systems are able to detect such covariation and adapt to reduce redundancy, leading to more efficient neural coding. Recent psychoacoustic studies have shown the auditory system can rapidly adapt to efficiently encode two covarying dimensions as a single dimension, following passive exposure to sounds in which temporal and spectral attributes covaried in a correlated fashion. However, these studies observed a cost to this adaptation, which was a loss of sensitivity to the orthogonal dimension. Here we explore the neural basis of this psychophysical phenomenon by recording single-unit responses from the primary auditory cortex in awake ferrets exposed passively to stimuli with two correlated attributes, similar in stimulus design to the psychoacoustic experiments in humans. We found: (1) the signal-to-noise ratio of spike-rate coding of cortical responses driven by sounds with correlated attributes remained unchanged along the exposure dimension, but was reduced along the orthogonal dimension; (2) performance of a decoder trained with spike data to discriminate stimuli along the orthogonal dimension was equally reduced; (3) correlations between neurons tuned to the two covarying attributes decreased after exposure; and (4) these exposure effects still occurred if sounds were correlated along two acoustic dimensions, but varied randomly along a third dimension. These neurophysiological results are consistent with the efficient coding hypothesis and may help deepen our understanding of how the auditory system encodes and represents acoustic regularities and covariance. [ABSTRACT FROM AUTHOR]

It has long been known from microneurographic recordings in human subjects that the activity of postganglionic sympathetic axons occurs as spontaneous bursts, with muscle sympathetic nerve activity (MSNA) exhibiting strong cardiac rhythmicity via the baroreflex and skin sympathetic nerve activity showing much weaker cardiac modulation. Here we review the firing properties of single sympathetic neurons, obtained using highly selective microelectrodes. Individual vasoconstrictor neurons supplying muscle or skin, or sudomotor neurons supplying sweat glands, always discharge with a low firing probability (~30%) and at very low frequencies (~0.5 Hz). Moreover, they usually fire only once per cardiac interval but can fire greater than four times within a burst. Modeling has shown that this pattern can best be explained by individual neurons being driven by, on average, two preganglionic inputs. Unitary recordings of muscle vasoconstrictor neurons have been made in several pathophysiological states, including heart failure, hypertension, obstructive sleep apnea, bronchiectasis, chronic obstructive pulmonary disease, depression, and panic disorder. The augmented MSNA in each of these diseases features an increase in firing probability and discharge frequency of individual muscle vasoconstrictor neurons above that seen in healthy subjects, yet firing rates rarely exceed 1 Hz. However, unlike patients with heart failure, all patients with respiratory disease or panic disorder, and patients with hyperhidrosis, exhibited an increase in multiple within-burst firing, which emphasizes the different modes by which the sympathetic nervous system grades its output in pathophysiological states of high sympathetic nerve activity. [ABSTRACT FROM AUTHOR]

The orbitofrontal cortex (OFC) and hippocampus (HC) are both implicated in forming the cognitive or task maps that support flexible behavior. Previously, we used the dopamine neurons as a sensor or tool to measure the functional effects of OFC lesions (Takahashi et al., 2011). We recorded midbrain dopamine neurons as rats performed an odor-based choice task, in which errors in the prediction of reward were induced by manipulating the number or timing of the expected rewards across blocks of trials. We found that OFC lesions ipsilateral to the recording electrodes caused prediction errors to be degraded consistent with a loss in the resolution of the task states, particularly under conditions where hidden information was critical to sharpening the predictions. Here we have repeated this experiment, along with computational modeling of the results, in rats with ipsilateral HC lesions. The results show HC also shapes the map of our task, however unlike OFC, which provides information local to the trial, the HC appears to be necessary for estimating the upper-level hidden states based on the information that is discontinuous or separated by longer timescales. The results contrast the respective roles of the OFC and HC in cognitive mapping and add to evidence that the dopamine neurons access a rich information set from distributed regions regarding the predictive structure of the environment, potentially enabling this powerful teaching signal to support complex learning and behavior.

Summary Sharp-wave ripples (SPW-Rs) in the hippocampus are implied in memory consolidation, as shown by observational and interventional experiments. However, the mechanism of their generation remains unclear. Using two-dimensional silicon probe arrays, we investigated the propagation of SPW-Rs across the hippocampal CA1, CA2, and CA3 subregions. Synchronous activation of CA2 ensembles preceded SPW-R-related population activity in CA3 and CA1 regions. Deep CA2 neurons gradually increased their activity prior to ripples and were suppressed during the population bursts of CA3-CA1 neurons (ramping cells). Activity of superficial CA2 cells preceded the activity surge in CA3-CA1 (phasic cells). The trigger role of the CA2 region in SPW-R was more pronounced during waking than sleeping. These results point to the CA2 region as an initiation zone for SPW-Rs. [ABSTRACT FROM AUTHOR]

Many speech sounds and animal vocalizations contain components, referred to as complex tones, that consist of a fundamental frequency (F0) and higher harmonics. In this study we examined single-unit activity recorded in the core (A1) and lateral belt (LB) areas of auditory cortex in two rhesus monkeys as they listened to pure tones and pitch-shifted conspecific vocalizations (‘coos’). The latter consisted of complex-tone segments in which F0 was matched to a corresponding pure-tone stimulus. In both animals, neuronal latencies to pure-tone stimuli at the best frequency (BF) were ~10 to 15 ms longer in LB than in A1. This might be expected, since LB is considered to be at a hierarchically higher level than A1. On the other hand, the latency of LB responses to coos was ~10 to 20 ms shorter than to the corresponding pure-tone BF, suggesting facilitation in LB by the harmonics. This latency reduction by coos was not observed in A1, resulting in similar coo latencies in A1 and LB. Multi-peaked neurons were present in both A1 and LB; however, harmonically-related peaks were observed in LB for both early and late response components, whereas in A1 they were observed only for late components. Our results suggest that harmonic features, such as relationships between specific frequency intervals of communication calls, are processed at relatively early stages of the auditory cortical pathway, but preferentially in LB.

Reciprocal connections between the orbitofrontal cortex (OFC) and the basolateral nucleus of the amygdala (BLA) provide a critical circuit for guiding normal behavior when information about expected outcomes is required. Recently, we reported that outcome signaling by OFC neurons is also necessary for learning in the face of unexpected outcomes during a Pavlovian over-expectation task. Key to learning in this task is the ability to build on prior learning to infer or estimate an amount of reward never previously received. OFC was critical to this process. Notably, in parallel work, we found that BLA was not necessary for learning in this setting. This suggested a dissociation in which the BLA might be critical for acquiring information about the outcomes but not for subsequently using it to make novel predictions. Here we evaluated this hypothesis by recording single-unit activity from BLA in rats during the same Pavlovian over-expectation task used previously.Wefound that spiking activity recorded in BLA in control rats did reflect novel outcome estimates derived from the integration of prior learning, however consistent with a model in which this process occurs in the OFC, these correlates were entirely abolished by ipsilateral OFC lesions. These data indicate that this information about these novel predictions is represented in the BLA, supported via direct or indirect input from the OFC, even though it does not appear to be necessary for learning. [ABSTRACT FROM AUTHOR]

Speech reception depends critically on temporal modulations in the amplitude envelope of the speech signal. Reverberation encountered in everyday environments can substantially attenuate these modulations. To assess the effect of reverberation on the neural coding of amplitude envelope, we recorded from single units in the inferior colliculus (IC) of unanesthetized rabbit using sinusoidally amplitude modulated (AM) broadband noise stimuli presented in simulated anechoic and reverberant environments. Although reverberation degraded both rate and temporal coding of AM in IC neurons, in most neurons, the degradation in temporal coding was smaller than the AM attenuation in the stimulus. This compensation could largely be accounted for by the compressive shape of the modulation input-output function (MIOF), which describes the nonlinear transformation of modulation depth from acoustic stimuli into neural responses. Additionally, in a subset of neurons, the temporal coding of AM was better for reverberant stimuli than for anechoic stimuli having the same modulation depth at the ear. Using hybrid anechoic stimuli that selectively possess certain properties of reverberant sounds, we show that this reverberant advantage is not caused by envelope distortion, static interaural decorrelation, or spectral coloration. Overall, our results suggest that the auditory system may possess dual mechanisms that make the coding of amplitude envelope relatively robust in reverberation: one general mechanism operating for all stimuli with small modulation depths, and another mechanism dependent on very specific properties of reverberant stimuli, possibly the periodic fluctuations in interaural correlation at the modulation frequency. [ABSTRACT FROM AUTHOR]

Auditory neurophysiology has demonstrated how basic acoustic features are mapped in the brain, but it is still not clear how multiple sound components are integrated over time and recognized as an object. We investigated the role of statistical learning in encoding the sequential features of complex sounds by recording neuronal responses bilaterally in the auditory forebrain of awake songbirds that were passively exposed to long sound streams. These streams contained sequential regularities, and were similar to streams used in human infants to demonstrate statistical learning for speech sounds. For stimulus patterns with contiguous transitions and with nonadjacent elements, single and multiunit responses reflected neuronal discrimination of the familiar patterns from novel patterns. In addition, discrimination of nonadjacent patterns was stronger in the right hemisphere than in the left, and may reflect an effect of top-down modulation that is lateralized. Responses to recurring patterns showed stimulus-specific adaptation, a sparsening of neural activity that may contribute to encoding invariants in the sound stream and that appears to increase coding efficiency for the familiar stimuli across the population of neurons recorded. As auditory information about the world must be received serially over time, recognition of complex auditory objects may depend on this type of mnemonic process to create and differentiate representations of recently heard sounds. [ABSTRACT FROM AUTHOR]

Many speech sounds and animal vocalizations contain components, referred to as complex tones, that consist of a fundamental frequency (F0) and higher harmonics. In this study we examined single-unit activity recorded in the core (A1) and lateral belt (LB) areas of auditory cortex in two rhesus monkeys as they listened to pure tones and pitch-shifted conspecific vocalizations ("coos"). The latter consisted of complex-tone segments in which F0 was matched to a corresponding pure-tone stimulus. In both animals, neuronal latencies to pure-tone stimuli at the best frequency (BF) were ~10 to 15 ms longer in LB than in A1. This might be expected, since LB is considered to be at a hierarchically higher level than A1. On the other hand, the latency of LB responses to coos was ~10 to 20 ms shorter than to the corresponding pure-tone BF, suggesting facilitation in LB by the harmonics. This latency reduction by coos was not observed in A1, resulting in similar coo latencies in A1 and LB. Multi-peaked neurons were present in both A1 and LB; however, harmonically-related peaks were observed in LB for both early and late response components, whereas in A1 they were observed only for late components. Our results suggest that harmonic features, such as relationships between specific frequency intervals of communication calls, are processed at relatively early stages of the auditory cortical pathway, but preferentially in LB. [ABSTRACT FROM AUTHOR]

Because the cardiovascular system and respiration are so intimately coupled, disturbances in respiratory control often lead to disturbances in cardiovascular control. Obstructive Sleep Apnoea (OSA), Chronic Obstructive Pulmonary Disease (COPD) and Bronchiectasis (BE) are all associated with a greatly elevated muscle vasoconstrictor drive (muscle sympathetic nerve activity; MSNA). Indeed, the increase in MSNA is comparable to that seen in congestive heart failure (CHF), in which the increase in MSNA compensates for the reduced cardiac output and thereby assists in maintaining blood pressure. However, in OSA – but not COPD or BE – the increase in MSNA can lead to hypertension. Here, the features of the sympathoexcitation in OSA, COPD and BE are reviewed in terms of the firing properties of post-ganglionic muscle vasoconstrictor neurones. Compared to healthy subjects with low levels of resting MSNA, single-unit recordings revealed that the augmented MSNA seen in OSA, BE, COPD and CHF were each associated with an increase in firing probability and mean firing rates of individual neurones. However, unlike patients with heart failure, all patients with respiratory disease exhibited an increase in multiple within-burst firing which, it is argued, reflects an increase in central sympathetic drive. Similar patterns to those seen in OSA, COPD and BE were seen in healthy subjects during an acute increase in muscle vasoconstrictor drive. These observations emphasise the differences by which the sympathetic nervous system grades its output in health and disease, with an increase in firing probability of active neurones and recruitment of additional neurones being the dominant mechanisms.

Postganglionic sympathetic axons in awake healthy human subjects, regardless of their identity as muscle vasoconstrictor, cutaneous vasoconstrictor or sudomotor neurones, discharge with a low firing probability (~30%), generate low firing rates (~0.5 Hz) and typically fire only once per cardiac interval. The purpose of the present study was to use modelling of spike trains in an attempt to define the number of preganglionic neurones that drive an individual postganglionic neurone. Artificial spike trains were generated in 1-3 preganglionic neurones converging onto a single postganglionic neurone. Each preganglionic input fired with a mean interval distribution of either 1000, 1500, 2000, 2500 or 3000 ms and the standard deviation varied between 0.5, 1.0 and 2.0 x the mean interval; the discharge frequency of each preganglionic neurone exhibited positive skewness and kurtosis. Of the 45 patterns examined, the mean discharge properties of the postganglionic neurone could only be explained by it being driven by, on average, two preganglionic neurones firing with a mean interspike interval of 2500 ms and SD of 5000 ms. The mean firing rate resulting from this pattern was 0.22 Hz, comparable to that of spontaneously active muscle vasoconstrictor neurones in healthy subjects (0.40 Hz). Likewise, the distribution of the number of spikes per cardiac interval was similar between the modelled and actual data: 0 spikes (69.5 vs 66.6 %), 1 spike (25.6 vs 21.2 %), 2 spikes (4.3 vs 6.4 %), 3 spikes (0.5 vs 1.7 %) and 4 spikes (0.1 vs 0.7 %). Although some features of the firing patterns could be explained by the postganglionic neurone being driven by a single preganglionic neurone, none of the emulated firing patterns generated by the firing of three preganglionic neurones matched the discharge of the real neurones. These modelling data indicate that, on average, human postganglionic sympathetic neurones are driven by two preganglionic inputs.

The hippocampus occupies a central role in mammalian navigation and memory. Yet an understanding of the rules that govern the statistics and granularity of the spatial code, as well as its interactions with perceptual stimuli, is lacking. We analyzed CA1 place cell activity recorded while rats foraged in different large-scale environments. We found that place cell activity was subject to an unexpected but precise homeostasis—the distribution of activity in the population as a whole being constant at all locations within and between environments. Using a virtual reconstruction of the largest environment, we showed that the rate of transition through this statistically stable population matches the rate of change in the animals' visual scene. Thus, place fields near boundaries were small but numerous, while in the environment's interior, they were larger but more dispersed. These results indicate that hippocampal spatial activity is governed by a small number of simple laws and, in particular, suggest the presence of an information-theoretic bound imposed by perception on the fidelity of the spatial memory system. [Display omitted] • Neural activity in rodent CA1 place cell populations is homeostatically balanced • Hippocampal place field size and frequency are governed by proximity to boundaries • Transition rate through place cell population matches rate of change in visual scene New work by Tanni, de Cothi, and Barry finds that place cell activity in the mammalian hippocampus is homeostatically controlled—the distribution of firing rates in the population is stable. During motion, the rate of transition through these cells matches the rate of change in the visual scene, yielding smaller, more numerous fields near walls. [ABSTRACT FROM AUTHOR]

Temporal pole (TP) cortex is associated with higher-order sensory perception and/or recognition memory, as human patients with damage in this region show impaired performance during some tasks requiring recognition memory (Olson et al. 2007). The underlying mechanisms of TP processing are largely based on examination of the visual nervous system in humans and monkeys, while little is known about neuronal activity patterns in the auditory portion of this region, dorsal TP (dTP; Poremba et al. 2003). The present study examines single-unit activity of dTP in rhesus monkeys performing a delayed matching-to-sample task utilizing auditory stimuli, wherein two sounds are determined to be the same or different. Neurons of dTP encode several task-relevant events during the delayed matching-to-sample task, and encoding of auditory cues in this region is associated with accurate recognition performance. Population activity in dTP shows a match suppression mechanism to identical, repeated sound stimuli similar to that observed in the visual object identification pathway located ventral to dTP (Desimone 1996; Nakamura and Kubota 1996). However, in contrast to sustained visual delay-related activity in nearby analogous regions, auditory delay-related activity in dTP is transient and limited. Neurons in dTP respond selectively to different sound stimuli and often change their sound response preferences between experimental contexts. Current findings suggest a significant role for dTP in auditory recognition memory similar in many respects to the visual nervous system, while delay memory firing patterns are not prominent, which may relate to monkeys' shorter forgetting thresholds for auditory vs. visual objects. [ABSTRACT FROM AUTHOR]

Despite extensive knowledge of its molecular and cellular effects, how anesthesia affects sensory processing remains poorly understood. In particular, it remains unclear whether anesthesia modestly or robustly degrades activity in primary sensory regions, and whether such changes are linked to anesthesia drug concentration versus behavioral unresponsiveness, which are typically confounded. Here, we used slow gradual intravenous propofol anesthesia induction together with auditory stimulation and intermittent assessment of behavioral responsiveness while recording epidural electroencephalogram, and neuronal spiking activity in primary auditory cortex (PAC) of eight rats. We found that all main components of neuronal activity including spontaneous firing rates, onset response magnitudes, onset response latencies, postonset neuronal silence duration, late-locking to 40 Hz click-trains, and offset responses, gradually changed in a dose-dependent manner with increasing anesthesia levels without showing abrupt shifts around loss of righting reflex or other time-points. Thus, the dominant factor affecting PAC responses is the anesthesia drug concentration rather than any sudden, dichotomous behavioral state changes. Our findings explain a wide array of seemingly conflicting results in the literature that, depending on the precise definition of wakefulness (vigilant vs. drowsy) and anesthesia (light vs. deep/surgical), report a spectrum of effects in primary regions ranging from minimal to dramatic differences., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The article discusses about the efficiency of renal denervation (RDN) in high blood pressure (BP) treatment and controlling muscle sympathetic nerve activity (MSNA). The study is performed through a baseline and a 3-month follow-up in 35 patients with resistant high blood pressure, where their BP and MSNA were evaluated. Results proved that RDN enables fast cut of single sympathetic vasoconstrictor fibers, making it an efficient hypertension treatment.

The literature on the neural basis of learning and memory is replete with studies using rats and monkey, but hardly any using pigeons. This is odd because so much of what we know about animal behavior comes from studies with pigeons. The unwillingness to use pigeons in neural studies of learning and memory probably stems from two factors, one that the avian brain is seen as radically different from the mammalian brain and as such can contribute little to its understanding, and the other that the behavior of pigeons is not seen as sophisticated as that of mammals, and certainly primates. Studies over the past few decades detailing the remarkable cognitive abilities of pigeons, as well as a newly revised nomenclature for the avian brain, should spark a renewed interest in using pigeons as models to understand the neural basis of learning and memory. Here we review studies on the pigeon's hippocampus and 'prefrontal cortex' and show that they provide information not only on the workings of the avian brain, but also shed light on the operation of the mammalian brain. [ABSTRACT FROM AUTHOR]

Because the cardiovascular system and respiration are so intimately coupled, disturbances in respiratory control often lead to disturbances in cardiovascular control. Obstructive Sleep Apnea (OSA), Chronic Obstructive Pulmonary Disease (COPD), and Bronchiectasis (BE) are all associated with a greatly elevated muscle vasoconstrictor drive (muscle sympathetic nerve activity, MSNA). Indeed, the increase in MSNA is comparable to that seen in congestive heart failure (CHF), in which the increase in MSNA compensates for the reduced cardiac output and thereby assists in maintaining blood pressure. However, in OSA - but not COPD or BE - the increase in MSNA can lead to hypertension. Here, the features of the sympathoexcitation in OSA, COPD, and BE are reviewed in terms of the firing properties of post-ganglionic muscle vasoconstrictor neurons. Compared to healthy subjects with low levels of resting MSNA, single-unit recordings revealed that the augmented MSNA seen in OSA, BE, COPD, and CHF were each associated with an increase in firing probability and mean firing rates of individual neurons. However, unlike patients with heart failure, all patients with respiratory disease exhibited an increase in multiple within-burst firing which, it is argued, reflects an increase in central sympathetic drive. Similar patterns to those seen in OSA, COPD, and BE were seen in healthy subjects during an acute increase in muscle vasoconstrictor drive. These observations emphasize the differences by which the sympathetic nervous system grades its output in health and disease, with an increase in firing probability of active neurons and recruitment of additional neurons being the dominant mechanisms. [ABSTRACT FROM AUTHOR]

Emotional learning requires the coordinated action of neural populations in limbic and cortical networks. Here, we performed simultaneous extracellular recordings from gustatory cortical (GC) and basolateral amygdalar (BLA) neural ensembles as awake, behaving rats learned to dislike the taste of saccharin [via conditioned taste aversion (CTA)]. Learning-related changes in single-neuron sensory responses were observed in both regions, but the nature of the changes was region specific. In GC, most changes were restricted to relatively late aspects of the response (starting ~ 1.0 s after stimulus administration), supporting our hypothesis that in this paradigm palatability-related information resides exclusively in later cortical responses. In contrast, and consistent with data suggesting the amygdala's primary role in judging stimulus palatability, CTA altered all components of BLA taste responses, including the earliest. Finally, learning caused dramatic increases in the functional connectivity (measured in terms of cross-correlation peak heights) between pairs of simultaneously recorded BLA and GC neurons, increases that were evident only during taste processing. Our simultaneous assays of the activity of single neurons in multiple relevant brain regions across learning suggest that the transmission of taste information through amygdala-- cortical circuits plays a vital role in CTA memory formation. [ABSTRACT FROM AUTHOR]

Episodic memories allow us to remember not only that we have seen an item before but also where and when we have seen it (context). Sometimes, we can confidently report that we have seen something (familiarity) but cannot recollect where or when it was seen. Thus, the two components of episodic recall, familiarity and recollection, can be behaviorally dissociated. It is not clear, however, whether these two components of memory are represented separately by distinct brain structures or different populations of neurons in a single anatomical structure. Here, we report that the spiking activity of single neurons in the human hippocampus and amygdala [the medial temporal lobe (MTL)] contain information about both components of memory. We analyzed a class of neurons that changed its firing rate to the second presentation of a previously novel stimulus. We found that the neuronal activity evoked by the presentation of a familiar stimulus (during retrieval) distinguishes stimuli that will be successfully recollected from stimuli that will not be recollected. Importantly, the ability to predict whether a stimulus is familiar is not influenced by whether the stimulus will later be recollected. We thus conclude that human MTL neurons contain information about both components of memory. These data support a continuous strength of memory model of MTL function: the stronger the neuronal response, the better the memory. [ABSTRACT FROM AUTHOR]

The article discusses a study which proposed a technique to record the firing patterns of gonadotropin-releasing hormone (GnRH) neurons in brain slices continuously for several hours. The study used mice that were transgenically engineered to express green fluorescent protein (GFP) in GnRH neurons using the murine GnRH promoter. GnRH neurons were viewed with an Olympus BX50WI upright fluorescent microscope equipped with infrared differential interference contrast.

A variety of studies have shown that motor cortical areas can be activated by observation of familiar actions. Here, we describe single-neuron responses in monkey primary motor (MI) and dorsal premotor (PMd) cortices during passive observation and execution of a familiar task. We show that the spiking modulation, preferred directions, and encoded information of cells in MI and PMd remain consistent during both observation and movement. Furthermore, we find that the presence of a visual target is necessary to elicit this congruent neural activity during observation. These findings along with results from our analysis of the oscillatory power in the beta frequency of the local field potential are consistent with previous imaging and EEG studies that have suggested that congruence between observation and action is a general feature of the motor system, even outside of canonical "mirror" areas. Such congruent activity has proposed relevance to motor learning, mimicry, and communication and has practical applications for the development of motorcortical neuroprostheses in paralyzed patients. [ABSTRACT FROM AUTHOR]

The effects of attention on neuronal responses in visual cortex have been likened to a change in stimulus contrast. Attention and stimulus contrast both modulate the magnitude of neuronal responses. However, changes in stimulus contrast also affect the latency of visual responses. Although many neurophysiological studies have examined how attention affects the strength of neuronal responses, few have considered whether attention affects neuronal latencies. To compare directly the effects of stimulus contrast and attention, we recorded responses from individual neurons in area V4 of macaque monkeys while they performed a task that independently controlled spatial attention and stimulus contrast. As expected, changes in stimulus contrast affected both the magnitude and latency of neuronal responses. Although attention had the expected effects on the magnitudes of neuronal responses, we did not detect statistically reliable changes in neuronal latency. A direct comparison of the effects of contrast and attention revealed a reliable difference. When a shift in spatial attention decreased response magnitude, response latency increased much less than when the same magnitude change was caused by reducing stimulus contrast. Thus, attention is distinct from contrast in the way it affects the relationship between neuronal response magnitude and latency. [ABSTRACT FROM AUTHOR]

The return to drug seeking, even after prolonged periods of abstinence, is a defining feature of cocaine addiction. The neural circuitry underlying relapse has been identified in neuropharmacological studies of experimental animals, typically rats, and supported in brain imaging studies of human addicts. Although the nucleus accumbens (NAcc), which has long been implicated in goal-directed behavior, plays a critical role in this circuit, the prefrontal cortex (PFC) appears to process the events that directly trigger relapse: exposure to acute stress, cues previously associated with the drug, and the drug itself. In this paper, we review animal models of relapse and what they have revealed about the mechanisms underlying the involvement of the NAcc and PFC in cocaine-seeking behavior. We also present electrophysiological data from PFC illustrating how the hedonic, motor, motivational, and reinforcing effects of cocaine can be analyzed at the neuronal level. Our preliminary findings suggest a role for PFC in processing information related to cocaine seeking but not the hedonic effects of the drug. Further use of this recording technology can help dissect the functions of PFC and other components of the neural circuitry underlying relapse. [ABSTRACT FROM AUTHOR]

Purpose:The present study examined the effect of electrical kindling on the interictal temporal response properties of single units recorded from primary auditory cortex (AI) of the adult cat.Methods:Cats were permanently implanted with electrodes in AI, kindled twice daily for 40 sessions, and the contralateral AI was subsequently mapped. Kindling stimulation consisted of 1-s trains of biphasic square-wave pulses applied at a frequency of 60 Hz, 100μA above the afterdischarge (AD) threshold. The EEG activity was recorded during each kindling session, and the behavioral manifestation was scored. Subsequent to kindling, multiple single-unit responses were recorded under ketamine anesthesia in response to 1-s-long periodic click trains, with click rates between 2 and 64 Hz. Neuronal responses were characterized according to their ability to respond in time-locked fashion to the clicks.Results:Kindling stimulation resulted in progression of the AD characteristics and seizure behavior, with six of 10 kindled cats reaching a fully generalized state. In the fully kindled cats, the best modulation frequencies and limiting following rates for the single-unit responses were significantly lower compared with those of naive and sham controls.Conclusions:Repeated epileptiform activity interferes with temporal processing in cat auditory cortex in the interictal state. This may have implications for people with epileptic foci in auditory-related areas. [ABSTRACT FROM AUTHOR]

This study compared the release behavior of single-unit (tablets, capsules) and multiple-unit (minitablets in capsules) controlled-release systems of furosemide. The swelling and erosion behaviors of these systems, which contained the swellable hydrophilic polymers sodium alginate (high viscosity) and Carbopol 974P, were compared. Swelling and erosion experiments showed a high degree of swelling and limited erosion for the Carbopol preparations, whereas less swelling but greater erosion was observed for the sodium alginate preparations. The sodium alginate preparations were eroded in 6 hours, while Carbopol preparations exhibited limited erosion within this period of time. These results appear to be attributed to the physicochemical characteristics of the polymers used in this study. Polymer characteristics greatly influenced the release of furosemide (model drug) from the formulations prepared and tested. Sodium alginate had a less pronounced sustained release effect compared with Carbopol (ie, in 8 hours all 3 sodium alginate dosage forms displayed complete release of furosemide, while only 30% of the drug was released from Carbopol dosage forms). Finally, all 3 Carbopol dosage forms (single- and multiple-unit) displayed similar release behavior while sodium alginate dosage forms displayed a different and more distinctive behavior. Minitablets and tablets showed a greater sustained release effect compared with capsules. Evaluation of the release data indicates that the release mechanism for sodium alginate formulations may be attributed to erosion/dissolution, while for Carbopol it may be attributed mainly to polymer relaxation and diffusion of the drug from the polymer surface. [ABSTRACT FROM AUTHOR]

Neuromodulation as a non‐drug alternative for managing visceral pain in irritable bowel syndrome (IBS) may target sensitized afferents of distal colon and rectum (colorectum), especially their somata in the dorsal root ganglion (DRG). Developing selective DRG stimulation to manage visceral pain requires knowledge of the topological distribution of colorectal afferent somata which are sparsely distributed in the DRG. Here, we implemented GCaMP6f to conduct high‐throughput optical recordings of colorectal afferent activities in lumbosacral DRG, that is, optical electrophysiology. Using a mouse ex vivo preparation with distal colorectum and L5‐S1 DRG in continuity, we recorded 791 colorectal afferents' responses to graded colorectal distension (15, 30, 40, and 60 mmHg) and/or luminal shear flow (20–30 mL/min), then functionally classified them into four mechanosensitive classes, and determined the topological distribution of their somata in the DRG. Of the 791 colorectal afferents, 90.8% were in the L6 DRG, 8.3% in the S1 DRG, and only 0.9% in the L5 DRG. L6 afferents had all four classes: 29% mucosal, 18.4% muscular‐mucosal, 34% low‐threshold (LT) muscular, and 18.2% high‐threshold (HT) muscular afferents. S1 afferents only had three classes: 19.7% mucosal, 34.8% LT muscular, and 45.5% HT muscular afferents. All seven L5 afferents were HT muscular. In L6 DRG, somata of HT muscular afferents were clustered in the caudal region whereas somata of the other classes did not cluster in specific regions. Outcomes of this study can directly inform the design and improvement of next‐generation neuromodulation devices that target the DRG to alleviate visceral pain in IBS patients. [ABSTRACT FROM AUTHOR]