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Author(s): Thomas Klausberger (corresponding author) [1]; Peter J. Magill [1]; László F. Márton [1]; J. David B. Roberts [1]; Philip M. Cobden [1]; György Buzsáki [2]; Peter Somogyi [1] Neural-network [...]

The primordial form of mammalian colour vision relies on opponent interactions between inputs from just two cone types, 'blue' (S-) and 'green' ( ML-) cones. We recently described the spatial receptive field structure of colour opponent blue- ON cells from the lateral geniculate nucleus of cats. Functional inputs from the opponent cone types were spatially coextensive and equally weighted, supporting their high chromatic and low achromatic sensitivity. Here, we studied relative cone weights, temporal frequency tuning and visual latency of cat blue- ON cells and non-opponent achromatic cells to temporally modulated cone-isolating and achromatic stimuli. We confirmed that blue- ON cells receive equally weighted antagonistic inputs from S- and ML-cones whereas achromatic cells receive exclusive ML-cone input. The temporal frequency tuning curves of S- and ML-cone inputs to blue- ON cells were tightly correlated between 1 and 48 Hz. Optimal temporal frequencies of blue- ON cells were around 3 Hz, whereas the frequency optimum of achromatic cells was close to 10 Hz. Most blue- ON cells showed negligible response to achromatic flicker across all frequencies tested. Latency to visual stimulation was significantly greater in blue- ON than in achromatic cells. The S- and ML-cone responses of blue- ON cells had on average, similar latencies to each other. Altogether, cat blue- ON cells showed remarkable balance of opponent cone inputs. Our results also confirm similarities to primate blue- ON cells suggesting that colour vision in mammals evolved on the basis of a sluggish pathway that is optimized for chromatic sensitivity at a wide range of spatial and temporal frequencies. [ABSTRACT FROM AUTHOR]

It has been proposed that the retrosplenial cortex forms part of a 'where/when' information network. The present study focussed on the related issue of whether retrosplenial cortex also contributes to 'what/when' information, by examining object recency memory. In Experiment 1, rats with retrosplenial lesions were found to be impaired at distinguishing the temporal order of objects presented in a continuous series ('Within-Block' condition). The same lesioned rats could, however, distinguish between objects that had been previously presented in one of two discrete blocks ('Between-Block' condition). Experiment 2 used intact rats to map the expression of the immediate-early gene c -fos in retrosplenial cortex following performance of a between-block, recency discrimination. Recency performance correlated positively with levels of c- fos expression in both granular and dysgranular retrosplenial cortex (areas 29 and 30). Expression of c -fos in the granular retrosplenial cortex also correlated with prelimbic cortex and ventral subiculum c -fos activity, the latter also correlating with recency memory performance. The combined findings from both experiments reveal an involvement of the retrosplenial cortex in temporal order memory, which includes both between-block and within-block problems. The current findings also suggest that the rat retrosplenial cortex comprises one of a group of closely interlinked regions that enable recency memory, including the hippocampal formation, medial diencephalon and medial frontal cortex. In view of the well-established importance of the retrosplenial cortex for spatial learning, the findings support the notion that, with its frontal and hippocampal connections, retrosplenial cortex has a key role for both what/when and where/when information. [ABSTRACT FROM AUTHOR]

Planning of multi-step actions based on the retrieval of acquired information is essential for efficient foraging. The hippocampus (HPC) and prefrontal cortex (PFC) may play critical roles in this process. However, in rodents, many studies investigating such roles utilized T-maze tasks that only require one-step actions (i.e., selection of one of two alternatives), in which memory retrieval and selection of an action based on the retrieval cannot be clearly differentiated. In monkeys, PFC has been suggested to be involved in planning of multi-step actions; however, the synchrony between HPC and PFC has not been evaluated. To address the combined role of the regions in planning of multi-step actions, we introduced a task in rats that required three successive nose-poke responses to three sequentially illuminated nose-poke holes. During the task, local field potentials (LFP) and spikes from hippocampal CA1 and medial PFC (mPFC) were simultaneously recorded. The position of the first hole indicated whether the following two holes would be presented in a predictable sequence or not. During the first nose-poke period, phase synchrony of LFPs in the theta range (4-10 Hz) between the regions was not different between predictable and unpredictable trials. However, only in trials of predictable sequences, the magnitude of theta phase synchrony during the first nose-poke period was negatively correlated with latency of the two-step ahead nose-poke response. Our findings point to the HPC-mPFC theta phase synchrony as a key mechanism underlying planning of multi-step actions based on memory retrieval rather than the retrieval itself. [ABSTRACT FROM AUTHOR]

The hypothalamic neuropeptide oxytocin ( OT) controls childbirth and lactation, is involved in social behaviors, plays a role in various psychiatric disorders, and has effects on learning and memory. Although behavioral effects of OT have been extensively studied, much less is known about its effects on neuronal and network activity patterns. Here, we investigate the effect of OT on two major patterns of hippocampal network activity in mouse hippocampal slices. We studied different in vitro models of gamma-frequency oscillations and sharp wave-ripple complexes ( SPW-R), two patterns implicated in spatial memory formation and memory consolidation respectively. Strikingly, we found a profound difference of OT on these distinct, mutually exclusive activity patterns. While gamma oscillations where not affected by the activation of hippocampal OT receptors, SPW-R were potently and rapidly suppressed. Interestingly, the temporal precision of oscillation-coupled spikes was enhanced at the same time. Thus, OT exerts strongly different modulatory effects on different network patterns, most likely by inhibition of different sets of inhibitory interneurons. The observed dichotomy between gamma and SPW-R oscillations may have profound effects on the behavioral and cognitive effects of OT which are relevant to cognitive processes and to psychiatric diseases. [ABSTRACT FROM AUTHOR]

Data obtained in in vitro experiments and urethane anaesthetized animals have revealed that the mechanisms responsible for the generation of hippocampal cholinergic theta rhythm are specifically affected by the administration of broad spectrum gap junctions ( GJs) blocker - carbenoxolone ( CBX). The aim of this study was to examine the effect of GJs modulation on the production of posterior hypothalamic theta. Specifically, we were interested in evaluating whether CBX could attenuate the theta rhythm recorded from the supramammillary nucleus and posterior hypothalamic nuclei, in both in vitro and in vivo preparations. The data we obtained from in vitro and in vivo preparations demonstrated that the administration of CBX did not suppress cholinergically induced theta in posterior hypothalamic area ( PHa) slices nor the theta rhythm observed in the PHa of urethane anaesthetized rats. Moreover, the application of trimethylamine, while very effective in the enhancement of hippocampal theta rhythm, did not produce any changes in theta oscillations observed in either in vitro or in vivo posterior hypothalamic area preparations. These data show that electrical coupling via GJs is not involved in theta rhythm generation in the PHa. Surprisingly, we observed a significant enhancement of theta activity in response to the carbenoxolone administration in both in vitro and in vivo PHa preparations. The theta rhythm enhancement detected in those experiments was attenuated by the application of spironolactone (mineralocorticoid receptors antagonist). We suggest that the observed excitatory effects of CBX on posterior hypothalamic oscillatory activity in the theta band could be mediated by mineralocorticoid receptors. [ABSTRACT FROM AUTHOR]

Atorvastatin has been shown to affect cognitive functions in rodents and humans. However, the underlying mechanism is not fully understood. Because hippocampal gamma oscillations (γ, 20-80 Hz) are associated with cognitive functions, we studied the effect of atorvastatin on persistent kainate-induced γ oscillation in the CA3 area of rat hippocampal slices. The involvement of NMDA receptors and multiple kinases was tested before and after administration of atorvastatin. Whole-cell current-clamp and voltage-clamp recordings were made from CA3 pyramidal neurons and interneurons before and after atorvastatin application. Atorvastatin increased γ power by ~ 50% in a concentration-dependent manner, without affecting dominant frequency. Whereas atorvastatin did not affect intrinsic properties of both pyramidal neurons and interneurons, it increased the firing frequency of interneurons but not that of pyramidal neurons. Furthermore, whereas atorvastatin did not affect synaptic current amplitude, it increased the frequency of spontaneous inhibitory post-synaptic currents, but did not affect the frequency of spontaneous excitatory post-synaptic currents. The atorvastatin-induced enhancement of γ oscillations was prevented by pretreatment with the PKA inhibitor H89, the ERK inhibitor U0126, or the PI3K inhibitor wortmanin, but not by the NMDA receptor antagonist D-AP5. Taken together, these results demonstrate that atorvastatin enhanced the kainate-induced γ oscillation by increasing interneuron excitability, with an involvement of multiple intracellular kinase pathways. Our study suggests that the classical cholesterol-lowering agent atorvastatin may improve cognitive functions compromised in disease, via the enhancement of hippocampal γ oscillations. [ABSTRACT FROM AUTHOR]

In rats, learning and memory performance decline during aging, which makes this rodent species a suitable model to evaluate therapeutic strategies of potential value for correcting age-related cognitive deficits. Some of these strategies involve neurotrophic factors like insulin-like growth factor-I ( IGF-I), a powerful neuroprotective molecule in the brain. Here, we implemented 18-day long intracerebroventricular ( ICV) IGF-I gene therapy in 28 months old Sprague-Dawley female rats, and assessed spatial memory performance in the Barnes maze. We also studied hippocampal morphology using an unbiased stereological approach. Adenovectors expressing the gene for rat IGF-I or the reporter DsRed were used. Cerebrospinal fluid ( CSF) samples were taken and IGF-I levels determined by radioimmunoassay. At the end of the study, IGF-I levels in the CSF were significantly higher in the experimental group than in the DsRed controls. After treatment, the IGF-I group showed a significant improvement in spatial memory accuracy as compared with DsRed counterparts. In the dentate gyrus ( DG) of the hippocampus, the IGF-I group showed a higher number of immature neurons than the DsRed controls. The treatment increased hippocampal astrocyte branching and reduced their number in the hippocampal stratum radiatum. We conclude that the ependymal route is an effective approach to increase CSF levels of IGF-I and that this strategy improves the accuracy of spatial memory in aging rats. The favorable effect of the treatment on DG neurogenesis and astrocyte branching in the stratum radiatum may contribute to improving memory performance in aging rats. [ABSTRACT FROM AUTHOR]