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Cholecystokinin (CCK) enables excitatory circuit long-term potentiation (LTP). Here, we investigated its involvement in the enhancement of inhibitory synapses. Activation of GABA neurons suppressed neuronal responses in the neocortex to a forthcoming auditory stimulus in mice of both sexes. High-frequency laser stimulation (HFLS) of GABAergic neurons potentiated this suppression. HFLS of CCK interneurons could induce the LTP of their inhibition toward pyramidal neurons. This potentiation was abolished in CCK knock-out mice but intact in mice with both CCK1R and 2R knockout of both sexes. Next, we combined bioinformatics analysis, multiple unbiased cell-based assays, and histology examinations to identify a novel CCK receptor, GPR173. We propose GPR173 as CCK3R, which mediates the relationship between cortical CCK interneuron signaling and inhibitory LTP in the mice of either sex. Thus, GPR173 might represent a promising therapeutic target for brain disorders related to excitation and inhibition imbalance in the cortex.SIGNIFICANCE STATEMENTCCK, the most abundant and widely distributed neuropeptide in the CNS, colocalizes with many neurotransmitters and modulators. GABA is one of the important inhibitory neurotransmitters, and much evidence shows that CCK may be involved in modulating GABA signaling in many brain areas. However, the role of CCK-GABA neurons in the cortical microcircuits is still unclear. We identified a novel CCK receptor, GPR173, localized in the CCK-GABA synapses and mediated the enhancement of the GABA inhibition effect, which might represent a promising therapeutic target for brain disorders related to excitation and inhibition imbalance in the cortex.

Plastic change in neuronal connectivity is the foundation of memory encoding. It is not clear whether the changes during anesthesia can alter subsequent behavior. Here, we demonstrated that in male rodents under anesthesia, a visual stimulus (VS) was associated with electrical stimulation of the auditory cortex or natural auditory stimulus in the presence of cholecystokinin (CCK), which guided the animals' behavior in a two-choice auditory task. Auditory neurons became responsive to the VS after the pairings. Moreover, high-frequency stimulation of axon terminals of entorhinal CCK neurons in the auditory cortex enabled LTP of the visual response in the auditory cortex. Such pairing during anesthesia also generated VS-induced freezing in an auditory fear conditioning task. Finally, we verified that direct inputs from the entorhinal CCK neurons and the visual cortex enabled the above neural plasticity in the auditory cortex. Our findings suggest that CCK-enabled visuoauditory association during anesthesia can be translated to the subsequent behavior action.SIGNIFICANCE STATEMENTOur study provides strong evidence for the hypothesis that cholecystokinin plays an essential role in the formation of cross-modal associative memory. Moreover, we demonstrated that an entorhinal–neocortical circuit underlies such neural plasticity, which will be helpful to understand the mechanisms of memory formation and retrieval in the brain.

Although fear memory formation is essential for survival and fear-related mental disorders, the neural circuitry and mechanism are incompletely understood. Here, we utilized trace fear conditioning to study the formation of trace fear memory in mice. We identified the entorhinal cortex (EC) as a critical component of sensory signaling to the amygdala. We adopted both loss-of-function and gain-of-function experiments to demonstrate that release of the cholecystokinin (CCK) from the EC is required for trace fear memory formation. We discovered that CCK-positive neurons project from the EC to the lateral nuclei of the amygdala (LA), and inhibition of CCK-dependent signaling in the EC prevented long-term potentiation of the auditory response in the LA and formation of trace fear memory. In summary, high-frequency activation of EC neurons triggers the release of CCK in their projection terminals in the LA, potentiating auditory response in LA neurons. The neural plasticity in the LA leads to trace fear memory formation.

A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-NTM) mice to investigate risk avoidance and found that these mice were impaired in risk avoidance on the elevated plus maze (EPM) and showed reduced social preference in a three-chamber social interaction test. Following EPM tests, c-Fos expression levels indicated that the nucleus accumbens (NAc) was associated with risk-avoidance behavior in DISC1-NTM mice. In addition, in vivo electrophysiological recordings following tamoxifen administration showed that the firing rates of fast-spiking neurons (FS) in the NAc were significantly lower in DISC1-NTM mice than in wild-type (WT) mice. In addition, in vitro patch clamp recording revealed that the frequency of action potentials stimulated by current injection was lower in parvalbumin (PV) neurons in the NAc of DISC1-NTM mice than in WT controls. The impairment of risk avoidance in DISC1-NTM mice was rescued using optogenetic tools that activated NAcPV neurons. Finally, inhibition of the activity of NAcPV neurons in PV-Cre mice mimicked the risk-avoidance impairment found in DISC1-NTM mice during tests on the elevated zero maze. Taken together, our findings confirm an impairment in risk avoidance in DISC1-NTM mice and suggest that reduced excitability of NAcPV neurons is responsible., Neuroscience Bulletin, 37 (9)

The Ornstein–Uhlenbeck neuronal model is specified by two types of parameters. One type corresponds to the properties of the neuronal membrane, whereas the second type (local average rate of the membrane depolarization and its variability) corresponds to the input of the neuron. In this article, we estimate the parameters of the second type from an intracellular record during neuronal firing caused by stimulation (audio signal). We compare the obtained estimates with those from the spontaneous part of the record. As predicted from the model construction, the values of the input parameters are larger for the periods when neuron is stimulated than for the spontaneous ones. Finally, the firing regimen of the model is checked. It is confirmed that the neuron is in the suprathreshold regimen during the stimulation.

In the mammalian brain, auditory information is known to be processed along a central ascending pathway leading to auditory cortex (AC). Whether there exist any major pathways beyond this canonical auditory neuraxis remains unclear. In awake mice, we found that auditory responses in entorhinal cortex (EC) cannot be explained by a previously proposed relay from AC based on response properties. By combining anatomical tracing and optogenetic/pharmacological manipulations, we discovered that EC received auditory input primarily from the medial septum (MS), rather than AC. A previously uncharacterized auditory pathway was then revealed: it branched from the cochlear nucleus, and via caudal pontine reticular nucleus, pontine central gray, and MS, reached EC. Neurons along this non-canonical auditory pathway responded selectively to high-intensity broadband noise, but not pure tones. Disruption of the pathway resulted in an impairment of specifically noise-cued fear conditioning. This reticular-limbic pathway may thus function in processing aversive acoustic signals.

Slow oscillations at frequencies

We investigated the firing pattern and frequency tuning properties of medial geniculate body (MGB) neurons, through in vivo intracellular recordings in anesthetized guinea pigs. Twenty-two of the 25 physiological characterized neurons were anatomically identified. Ten neurons were located in the ventral division of the medial geniculate body (MGv) (seven in pars ovoidea (OV) and three in the pars lateralis (LV)). Eight were located in the dorsal division (MGd), and four in the medial division (MGm). OV neurons showed a uniform, phasic ON response with high frequency selectivity. Functionally, they are interpreted as relaying spectral information with high reliability. LV neurons exhibited various patterns: phasic, tonic and excitatory postsynaptic potentials (EPSP) with a spike train. These high magnitude EPSPs are proposed to convey temporal information of the auditory signals with more encoding power. MGd neurons had relatively low best frequencies while MGm neurons had high intensity threshold, broader frequency selectivity, and a tonic response pattern. Tonic firing is likely to impose a strong impact onto wide cortical area and amygdala. When hyperpolarized with current injection, MGB neurons evoked low-threshold calcium spikes. Distinct change in these spike numbers was observed among MGv and MGd neurons as compared with MGm neurons, implying their differential roles. MGm neurons are more modulatory in nature, while the long lasting bursts of low-threshold calcium spikes observed in MGv and MGd neurons probably participate in propagating the sleep oscillations.

To investigate the corticofugal modulation of acoustic information ascending through the auditory pathway of the rat, immunohistochemical techniques were used to study the functional expression of Fos protein in neurons. With auditory stimulation at different frequencies, Fos expression in the medial geniculate body (MGB), inferior colliculus (IC), superior olivary complex, and cochlear nucleus was examined, and the extent of Fos expression on the two sides was compared. Strikingly, we found densely Fos-labeled neurons in all divisions of the MGB after both presentation of an auditory stimulus and administration of a gamma-aminobutyric acid type A (GABA(A)) antagonist (bicuculline methobromide; BIM) to the auditory cortex. The location of Fos-labeled neurons in the ventral division (MGv) after acoustic stimulation at different frequencies was in agreement with the known tonotopic organization. That no Fos-labeled neurons were found in the MGv with acoustic stimuli alone suggests that the transmission of ascending thalamocortical information is critically governed by corticofugal modulation. The dorsal (DCIC) and external cortices (ECIC) of the IC ipsilateral to the BIM-injected cortex showed a significantly higher number of Fos-labeled neurons than the contralateral IC. However, no difference in the number of Fos-labeled neurons was found between the central nucleus of the IC on either side, indicating that direct corticofugal modulation occurs only in the ECIC and DCIC. Further investigations are needed to assess the functional implications of the morphological differences observed between the descending corticofugal projections to the thalamus and the IC.

The neuronal interconnections between thalamus and cortex modulate information transmission in the central auditory system. To facilitate the understanding of its modulation effects and mechanism, first, the recent progress on investigating the anatomical connections and the physiological properties of the medial geniculate body and auditory cortex is summarized. Second, the connectional pattern and functional organization in thalamocortical and corticothalamic network are described. Third, the strategic position and role of the thalamic reticular nucleus in the auditory system are demonstrated. Lastly, the functional implication of this integrated system and possible interactions between auditory thalamus and cortex are discussed. The thalamocortical and corticothalamic projections may work as a dynamic filter array in integrating sensory information and optimizing signal processing in the auditory system.

In the present article, we summarize the recent progress on investigating the mechanism of corticofugal modulation on the auditory thalamus of mammals excluding the bat as it has a specialized auditory system. The article comprises: (1) a review of the anatomy and physiology of the auditory thalamus, and a discussion of (2) the corticofugal modulation of the lemniscal nucleus of the medial geniculate body (MGB), (3) modulation of the non-lemniscal MGB, (4) modulation of the specific responses to acoustic signals with various parameters, such as the sound intensity and the onset and offset of the stimulus, and, finally, (5) the possible function of the corticofugal system in the auditory attention.

on and off auditory responses were examined in the medial geniculate body (MGB) of the guinea pig. Single- and multiunit recordings were carried out on 12 anesthetized animals, and noise-burst or pure-tone stimuli were applied to the ear contralateral to the recording hemisphere. One hundred and thirty-fiveoff or on-off neurons and 160 onneurons were studied, and the tuning curves of 21 on-off oroff neurons were examined from various nuclei of the MGB. The mean minimum threshold of the off responses (40.8 ± 20.0 dB SPL, mean ± SD; range: 0–80 dB SPL) was significantly higher than that of the on responses (28.5 ± 17.6 dB SPL, range: 0–60 dB SPL; n = 17, P < 0.001). Of 10 on-off neurons that showed identifiable tuning frequencies for both on andoff responses, 7 showed a higher off thanon best frequency (BF), 2 showed the same BF for bothon and off, and only 1 showed a slightly loweroff than on BF. Most off responses sampled from the borders of the ventral (MGv) and the rostromedial (MGrm) nuclei of the MGB showed single-peaked tuning curves, similar to those of the on responses in the MGv. The neurons located in the shell (MGs) and dorsal (MGd) nuclei of the MGB showed complicated—either multi-peaked or broad—tuning curves. Alloff responses showed long-duration-selectivity for acoustic stimuli: the mean half-maximum duration was 116.5 ± 114.8 ms ( n = 19, range: 27–411 ms). The latencies of 135off responses were studied in various divisions of the MGB. The ventral border region of MGv showed the shortest latency, followed by the dorsal border region of the MGv, the MGrm, and the caudomedial nucleus (MGcm) of the MGB. The posterior nucleus of the thalamus (Po), the MGd, and the MGs showed much longer mean latencies of >30 ms ( P < 0.05 compared with the border regions of the MGv, ANOVA), with Po showing the greatest mean latency of 60.3 ms and the greatest deviation of 25.5 ms). The latency of the offresponse (29.0 ± 14.0 ms, n = 135) was significantly greater than that of the on response (15.6 ± 9.6 ms, n = 160, P < 0.001). The present results provide valuable information about the threshold, frequency tuning characteristics, minimal response latency, and duration selectivity of off neurons in the auditory thalamus.

The present study examined the anatomic connections of the dorsal zone of cat auditory cortex (DZ). The DZ was discriminated physiologically from the primary auditory field (AI) on the basis of neuronal responses with long latency and broad or multipeaked tuning curves. Wheat germ agglutinin-horseradish peroxidase was then injected either by pressure or iontophoretically. The thalamocortical and corticothalamic connections of the DZ were visualized by the presence of retrogradely labeled neurons and anterogradely labeled terminal fields in the thalamus; ipsilateral corticocortical projections from other cortical fields were visualized by the presence of retrogradely labeled cells. Injections of tracer into the DZ retrogradely labeled cells mainly in the lateral division of posterior complex (Po) and in the dorsal division (MGd) of the medial geniculate body (MGB); fewer labeled cells were found in the ventral (MGv) and medial (MGm) divisions of the MGB and in the suprageniculate nucleus. The DZ projection to Po, MGv, and MGd was heavy and was more diffuse than the reciprocal thalamocortical projection; the projection to MGm was light. The corticothalamic terminations and thalamocortical cells projecting to the same part of the DZ were not superimposed rigidly. The DZ received cortical projections from AI and from the second, anterior, and posterior auditory fields, and there were strong intra-DZ connections. Together with the physiological findings, the present results suggest that the DZ is a potentially separate auditory field from AI and is likely to be involved in both temporal and spectral integration of acoustic information. J. Comp. Neurol. 400:334‐348, 1998. r 1998 Wiley-Liss, Inc. Indexing terms: medial geniculate body; dorsal division; lateral division of the posterior thalamic complex; wheat germ agglutinin-horseradish peroxidase; reciprocal connections; thalamus

Tonotopic maps, obtained from single and multi-unit recordings in the primary and surrounding areas of the auditory cortex, were related to chemoarchitecture of the supratemporal plane, as delineated by immunoreactivity for parvalbumin. Neurons in the central core were sharply tuned and formed two complete tonotopic representations corresponding to the primary auditory area (AI) and the rostral (R) area. High frequencies were represented posteriorly in AI and anteriorly in R, the representation reversing in the anterior part of the core. Neurons in regions of less dense immunostaining previously described as lateral (L) and posteromedial (P-m) fields, showed broader frequency tuning. Two tonotopic representations were found in L: in an anterolateral (AL) field, corresponding to a field previously reported by others, high frequencies were represented anteriorly and low frequencies posteriorly; in a posterolateral field (PL) the trend reversed. There was a further reversal on entering P-m from the high frequency representation in PL and progressively lower frequencies tended to be represented more medially in P-m, but P-m may contain two representations reported by others. Neurons in the previously described anteromedial (A-m) and medial (M) fields of weaker immunostaining, were even more broadly tuned. A tonotopic progression from low frequency representation posteriorly to high frequency representation anteriorly was observed in the medial field. Frequency representation in A-m remains uncertain. No tonotopic representation could be demonstrated with the stimuli used in the zones of very weak parvalbumin immunostaining outside AL, PL, P-m, A-m, and M. The properties of neurons in the core and surrounding zones are likely to reflect inputs from the ventral and dorsal medial geniculate nuclei, respectively. The fields outside the core seem to be the starting points for separate streams of auditory corticocortical connections passing into association cortex. J. Comp. Neurol. 386:304–316, 1997. © 1997 Wiley-Liss, Inc.

In the present study, the sources of thalamic and cortical inputs of thalamic reticular nucleus (TRN) neurons were examined by investigating the responses of the TRN neurons to electrical stimulation of different sites in the thalamus and the cortex of the rat. The recurrent excitation of the corticothalamic system that is triggered by electrical stimulation was eliminated by ablating the auditory cortex and by temporarily inactivating the medial geniculate body (MGB), when studying the sources of thalamic and cortical inputs, respectively. Single TRN neurons responded to electrical stimulation of 50–100 μA of the thalamus over a large area (dorsoventrally 1.2–2.4 mm and mediolaterally 1.0–2.3 mm, n=9). Four of 16 auditory TRN neurons responded to electrical stimulation of the lateral geniculate nucleus. The TRN neurons responded to cortical stimulation over a rostrocaudal distance of 2.6±0.5 mm (range: 1.5–3.5 mm, n=24) of the auditory cortex. Visual or auditory TRN neurons also responded to electrical stimulation in the auditory or visual cortices, respectively. The present study revealed that each TRN neuron received a wide range of inputs from both ascending thalamic and descending cortical projections. The projection could be cross-modal. Having a strong and lasting inhibition on the thalamus, the TRN neurons are likely to be involved in adjusting global states relating to awareness and attention in the thalamocortical system.

Responses to repeated auditory stimuli were examined in 103 neurons in the auditory region of the thalamic reticular nucleus (TRN) and in 20 medial geniculate (MGB) neurons of anesthetized rats. A further six TRN neurons were recorded from awake rats. The TRN neurons showed strong responses to the first trial and weak responses to the subsequent trials of repeated auditory stimuli and electrical stimulation of the MGB and auditory cortex when the interstimulus interval (ISI) was short (

Expression of c-fos in the medial geniculate body (MGB) and the inferior colliculus (IC) in response to bicuculline-induced corticofugal activation was examined in rats at different time points after bilateral cochlear ablation (4 h-30 days). Corticofugal activation was crucial in eliciting Fos expression in the MGB after cochlear ablation. The pars ovoidea (OV) of the medial geniculate body ventral division (MGv) showed dense Fos expression 4 h after cochlear ablation; the expression declined to very low levels at 24 h and thereafter. In turn, strong Fos expression was found in the pars lateralis (LV) of the MGv 24 h after cochlear ablation and dropped dramatically at 14 days. The dorsal division of the MGB (MGd) showed high Fos expression 7 days after cochlear ablation, which persisted for a period of time. Using multi-electrode recordings, neuronal activity of different MGB subnuclei was found to correlate well with Fos expressions. The temporal changes in cortically activated Fos expression in different MGB subnuclei after bilateral cochlear ablation indicate differential denervation hypersensitivities of these MGB neurons and likely point to differential dependence of these nuclei on both auditory ascending and corticofugal descending inputs. After bilateral cochlear ablation, significant increases in Fos-positive neurons were detected unilaterally in all IC subnuclei, ipsilateral to the bicuculline injection.

Electrical stimulation of the auditory cortex (AC) causes both facilitatory and inhibitory effects on the medial geniculate body (MGB). The purpose of this study was to identify the corticofugal inhibitory pathway to the MGB. We assessed two potential circuits: 1) the cortico-colliculo-thalamic circuit and 2) cortico-reticulo-thalamic one. We compared intracellular responses of MGB neurons to electrical stimulation of the AC following bilateral ablation of the inferior colliculi (IC) or thalamic reticular nucleus (TRN) in anesthetized guinea pigs. Cortical stimulation with intact TRN could cause strong inhibitory effects on the MGB neurons. The corticofugal inhibition remained effective after bilateral IC ablation, but it was minimized after the TRN was lesioned with kainic acid. Synchronized TRN neuronal activity and MGB inhibitory postsynaptic potentials (IPSPs) were observed with multiple recordings. The results suggest that corticofugal inhibition traverses the corticoreticulothalamic pathway, indicating that the colliculi-geniculate inhibitory pathway is probably only for feedforward inhibition.

We investigated the firing pattern and frequency tuning properties of medial geniculate body (MGB) neurons, through in vivo intracellular recordings in anesthetized guinea pigs. Twenty-two of the 25 physiological characterized neurons were anatomically identified. Ten neurons were located in the ventral division of the medial geniculate body (MGv) (seven in pars ovoidea (OV) and three in the pars lateralis (LV)). Eight were located in the dorsal division (MGd), and four in the medial division (MGm). OV neurons showed a uniform, phasic ON response with high frequency selectivity. Functionally, they are interpreted as relaying spectral information with high reliability. LV neurons exhibited various patterns: phasic, tonic and excitatory postsynaptic potentials (EPSP) with a spike train. These high magnitude EPSPs are proposed to convey temporal information of the auditory signals with more encoding power. MGd neurons had relatively low best frequencies while MGm neurons had high intensity threshold, broader frequency selectivity, and a tonic response pattern. Tonic firing is likely to impose a strong impact onto wide cortical area and amygdala. When hyperpolarized with current injection, MGB neurons evoked low-threshold calcium spikes. Distinct change in these spike numbers was observed among MGv and MGd neurons as compared with MGm neurons, implying their differential roles. MGm neurons are more modulatory in nature, while the long lasting bursts of low-threshold calcium spikes observed in MGv and MGd neurons probably participate in propagating the sleep oscillations.

In the present study, we investigated the auditory responses of the medial geniculate (MGB) neurons, throughin vivointracellular recordings of anesthetized guinea pigs, while the auditory cortex was electrically activated. Of the 63 neurons that received corticofugal modulation of the membrane potential, 30 received potentiation and 33 received hyperpolarization. The corticofugal potentiation of the membrane potential (amplitude, mean ± SD, 8.6 ± 5.5 mV; duration, 125.5 ± 75.4 msec) facilitated the auditory responses and spontaneous firing of the MGB neurons. The hyperpolarization of –11.3 ± 4.9 mV in amplitude and 210.0 ± 210.1 msec in duration suppressed the auditory responses and spontaneous firing of the MGB neurons. Four of the five neurons that were histologically confirmed to be located in the lemniscal MGB received corticofugal facilitatory modulation, and all of the four neurons that were confirmed to be located in the non-lemniscal MGB received corticofugal inhibitory modulation. The present intracellular recording provides novel results on how the corticofugal projection gates the sensory information in the thalamus: via the spatially selective depolarization of lemniscal MGB neurons and hyperpolarization of non-lemniscal MGB neurons. It is speculated that the systematic selectivity of facilitation and inhibition over the lemniscal and non-lemniscal MGB is related to the attention shift within the auditory modality and across the sensory modalities.

In the present study, we investigated the oscillatory behavior of the auditory thalamic neurons throughin vivointracellular and extracellular recordings in anesthetized guinea pigs. Repeated acoustic stimulus and cortical electrical stimulation were applied to examine their modulatory effects on the thalamic oscillation. The time course of the spike frequency over each trial was obtained by summing all spikes in the onset period and/or the last time period of 100 or 200 msec in the raster display. Spectral analysis was made on the time course of the spike frequency. A slow-frequency oscillation ranging from 0.03 to 0.25 Hz (mean ± SD, 0.11 ± 0.05 Hz) was found in the medial geniculate body (MGB) together with a second rhythm of 5-10 Hz. The oscillation neurons had a mean auditory response latency of 17.3 ± 0.3 msec, which was significantly longer than that of the non-oscillation neurons in lemniscal MGB (9.0 ± 1.5 msec,p< 0.001, ANOVA) and similar to the non-oscillation neurons in the non-lemniscal MGB (17.6 ± 5.4 msec,p= 0.811). They were located in the non-lemniscal nuclei of the auditory thalamus. Cortical stimulation altered the thalamic oscillation, leading to termination of the oscillation or to acceleration of the rhythm of the oscillation (the average rhythm changed from 0.07 ± 0.03 to 0.11 ± 0.04 Hz,n= 8,p= 0.066,ttest). Acoustic stimulation triggered a more regular rhythm in the oscillation neurons. The present results suggest that only the non-lemniscal auditory thalamus is involved in the slow thalamocortical oscillation. The auditory cortex may control the oscillation of the auditory thalamic neurons.

Corticofugal modulation on both on andoff responses in various nuclei in the medial geniculate body (MGB) was examined by locally activating the auditory cortex and looking for effects on the neuronal responses to acoustic stimuli. In contrast with a major corticofugal facilitatory effect on theon neurons in the lemniscal nucleus of the MGB of the guinea pigs, of 132 on neurons tested in three conditions with cortical activation through each of three implanted electrodes, the majority of the tested conditions (319/396) that were sampled from the nonlemniscal nuclei of the MGB received inhibitory modulation from the activated cortex. This inhibitory effect was >50% for 99 cases while the auditory cortex was activated. Most of the offand on-off MGB neurons (44/54) showed a facilitatory effect of 111.4 ± 99.9%, and three showed a small inhibitory effect of 25.7 ± 5.8% on their off responses. Thirty neurons in the border region between the lemniscal and nonlemniscal MGB showed mainly facilitatory corticofugal effects on both on andoff responses. Meanwhile, cortical stimulation induced almost exclusive inhibitory effects on the on response and facilitatory effects on the off response in the MGcm. It is suggested that the off response is produced as a disinhibition from the inhibitory input of the auditory stimulus. The present results provide a possible explanation for selective gating of the auditory information through the lemniscal MGB while switching off other unwanted sensory signals and the interference from the limbic system, leaving the other auditory cortex prepared to process only the auditory signal.

ON and OFF auditory responses were examined on the medial geniculate body (MGB) of the guinea pig. Single-unit and multiunit recordings were performed on 13 anesthetized subjects while either noise-burst or pure-tone stimuli were applied to the ear contralateral to the recorded hemisphere. Of 2187 uneven-spaced samples, 1142 were ON neurons, 386 were OFF neurons, and 488 were ON-OFF neurons. Neither ON nor OFF neurons changed their response patterns when the stimulus was changed from a noise burst of 60 dB sound pressure level intensity (expressed in decibels per 20 mPa) to pure tones or noise bursts of other intensities. However, most of the ON-OFF neurons changed to either ON or OFF responses with some stimuli. OFF neurons formed clusters. With anatomical confirmation, we found that OFF neuron clusters are always segregated from ON neuron clusters and form OFF sheets in various divisions of the MGB. In the ventral division of the MGB (MGv), the neurons showed mainly ON responses in its core and OFF responses in its periphery or on its boundary with other divisions. The MGv was partially surrounded by an OFF sheet dorsolaterally at the caudal part and medioventrally at the rostral part and was almost completely surrounded by an OFF sheet at the central level rostrocaudally.

He, Jufang. Modulatory effects of regional cortical activation on the onset responses of the cat medial geniculate neurons. J. Neurophysiol. 77: 896–908, 1997. Corticofugal modulation on activity of the medial geniculate body (MGB) was examined by locally activating the primary auditory cortex (AI) and looking for effects on the onset responses of MGB neurons to acoustic stimuli. Of 103 MGB neurons recorded from 13 hemispheres of 11 animals, 91 neurons (88%) showed either a facilitatory or inhibitory effect or both; of these neurons, 72 showed facilitatory effects and 25 inhibitory effects. The average facilitatory effect was large, with a mean increase of 62.4%. Small inhibitory effects (mean: −16.2%) were obtained from a few neurons (6 of 103) when a pure tone stimulus was used, whereas the effect became larger and more frequent when a noise burst stimulus was used (mean: −27.3%, n = 22 of 27 neurons). Activation of an AI site having the same best frequency (BF) as the MGB neuron being recorded from produced mainly a facilitatory effect on MGB neuronal responses to pure tones. Activation of AI at a site neighboring the BF site produced inhibitory effects on the MGB response when noise burst stimuli were used. We found that the effective stimulation sites in AI that could modulate MGB activity formed patchlike maps with a diameter of 1.13 ± 0.09 (SE) mm (range 0.6–1.9 mm, n = 15) being larger than the patches of thalamocortical terminal fields. Examining the effects of sound intensities, of 18 neurons tested 9 neurons showed a larger effect for low-sound-intensity stimuli and small or no effects for high-sound-intensity stimuli. These were named low-sound-intensity effective neurons. Five neurons showed high sound intensity effectiveness and four were non-intensity specific. Most low-sound-intensity effective neurons were monotonic rate-intensity function neurons. The AI cortical modulatory effect was frequency specific, because 15 of 27 neurons showed a larger facilitatory effect when a BF stimulus was used rather than a stimulus of any other frequency. The corticothalamic connection between the recording site in MGB and the most effective stimulation site in AI was confirmed by injecting wheat germ agglutinin–horseradish peroxidase tracer at the stimulation site and producing a small lesion in the recording site. The results suggest that 1) the large facilitation effects obtained by AI activation at the region that directly projected to the MGB could be the result mainly of the direct projection terminals to the MGB relay neurons; 2) the large size patches of the effective stimulation site in AI could be due to widely ramifying corticothalamic projections; and 3) the corticofugal projection selectively gates auditory information mainly by a facilitatory effect, although there is also an inhibitory effect that depends on the sound stimulus used.

The intrinsic electrophysiological properties of medial geniculate body (MGB) neurons and their responses to noise bursts/pure tones were examined in the pentobarbital anesthetized guinea pig through intracellular recording. Discharge rate was calculated in the absence of acoustic stimuli over varied membrane potentials which were changed by intracellular injection of current or through automatic drifting. The non-acoustically-driven firing rate was 45.8±23.3 Hz (mean±S.D., n =8) at membrane potentials of −45 mV, 30.6±19.4 Hz ( n =14) at −50 mV, 18.0±12.9 Hz ( n =14) at −55 mV, and significantly decreased to 5.7±7.4 Hz at −60 mV, and to 0.7±1.5 Hz ( n =10) at −65 mV (ANOVA, P P t -test) than those associated with the putative LTS bursts (6.7±2.4 ms, P t -test). The dependence of the temporal structure of the spikes/spike bursts on the stimulus may provide insight into the temporal coding of sound information in the auditory system.

The medial geniculate body (MGB) of the auditory thalamus comprises lemniscal and nonlemniscal neurons that project to the primary auditory cortex and limbic structures, respectively. Here we show that in anesthetized guinea pigs, MGB responses to a noise-burst stimulus exhibit distinct and synaptic pathway-specific firing patterns. The majority of nonlemniscal MGB cells exhibited bursting responses, whereas lemniscal neurons discharged mainly single or spike doublets. The burst firing is delayed in nonlemniscal neurons and exhibited several features that are characteristics of those mediated by low-threshold Ca2+ spikes. Such a synaptic pathway-specific allocation of bursting and single-spike firing patterns is consistent with the notion of parallel processing of auditory information in thalamocortical system.

The present study examined auditory cortical neurons, the responses of which depended on the duration of noise bursts. We recorded from 150 neurons with response latencies exceeding 30 msec and from 28 neurons with OFF responses to auditory stimuli in the dorsal zone of cat auditory cortex. Of 150 long-latency neurons, 132 displayed some form of duration selectivity. Seventy-eight were classified as selective for long durations. Among the long-duration-selective neurons, 30 responded only to noise burst stimuli with durations longer than a minimal threshold and were classified further as duration threshold neurons. Of 132 duration-selective neurons, 41 responded selectively to noise bursts of short duration; 13 showed maximal responses to noise bursts of a particular duration and could be regarded as duration-tuned neurons. OFF-response neurons included ones that were long-duration-selective, duration-tuned, and nonduration-selective.Duration tuning has been described previously only at the midbrain level in amphibians and bats. The present finding of sensitivity to sound duration in at least one region of cat auditory cortex indicates that this form of neural tuning may be important for hearing in all vertebrates, and for processing of sound at multiple levels in the auditory pathway. The duration tuning in the cat auditory cortex was much broader, and the best duration was distributed over a wider range than in the bat inferior colliculus. We suggest that the duration selectivity of the long-latency neurons results from integration along the time domain of a stimulus during the latent period.

In the present study, we investigated the point-to-point modulatory effects from the auditory cortex to the thalamus in the guinea pig. Corticofugal modulation on thalamic neurons was studied by electrical activation of the auditory cortex. The modulation effect was sampled along the frontal or sagittal planes of the auditory thalamus, focusing on the ventral division (MGv) of the medial geniculate body (MGB). Electrical activation was targeted at the anterior and dorsocaudal auditory fields, to which the MGv projects and from which it assumptively receives reciprocal projections. Of the 101 MGv neurons examined by activation of the auditory cortex through passing pulse trains of 100–200 μA current into one after another of the three implanted electrodes (101 neurons × 3 stimulation sites = 303 cases), 208 cases showed a facilitatory effect, 85 showed no effect, and only 10 cases (7 neurons) showed an inhibitory effect. Among the cases of facilitation, 63 cases showed a facilitatory effect >100%, and 145 cases showed a facilitatory effect from 20–100%. The corticofugal modulatory effect on the MGv of the guinea pig showed a widespread, strong facilitatory effect and very little inhibitory effect. The MGv neurons showed the greatest facilitations to stimulation by the cortical sites, with the closest correspondence in BF. Six of seven neurons showed an elevation of the rate-frequency functions when the auditory cortex was activated. The comparative results of the corticofugal modulatory effects on the MGv of the guinea pig and the cat, together with anatomical findings, hint that the strong facilitatory effect is generated through the strong corticothalamic direct connection and that the weak inhibitory effect might be mainly generated via the interneurons of the MGv. The temporal firing pattern of neuronal response to auditory stimulus was also modulated by cortical stimulation. The mean first-spike latency increased significantly from 15.7 ± 5.3 ms with only noise-burst stimulus to 18.3 ± 4.9 ms ( n = 5, P < 0.01, paired t-test), while the auditory cortex was activated with a train of 10 pulses. Taking these results together with those of previous experiments conducted on the cat, we speculate that the relatively weaker inhibitory effect compared with that in the cat could be due to the smaller number of interneurons in the guinea pig MGB. The corticofugal modulation of the firing pattern of the thalamic neurons might enable single neurons to encode more auditory information using not only the firing rate but also the firing pattern.