The hippocampus is a key brain circuit for spatial memory, and the spatially-selective spiking of hippocampal neuronal assemblies is thought to provide a mnemonic representation of space. Here we show that remembering newly-learnt goal locations requires the NMDA receptor-dependent stabilization and enhanced reactivation of goal-related hippocampal assemblies. During spatial learning, place-related firing patterns in the CA1, but not CA3, region of the rat hippocampus were reorganized to represent new goal locations. Such reorganization did not occur when goals were marked by visual cues. The stabilization and successful retrieval of these newly-acquired CA1 representations for behaviorally-relevant places was NMDAR-dependent and necessary for subsequent memory retention performance. Goal-related assembly patterns associated with sharp wave/ripple network oscillations, during both learning and subsequent rest periods, predicted memory performance. Together, these results suggest that reorganization and reactivation of assembly firing patterns in the hippocampus represent the formation and expression of new spatial memory traces.

In the hippocampal CA1 area, a relatively homogenous population of pyramidal cells is accompanied by a diversity of GABAergic interneurons. Previously, we found that parvalbumin-expressing basket, axo-axonic, bistratified, and oriens-lacunosum moleculare cells, innervating different domains of pyramidal cells, have distinct firing patterns during network oscillations in vivo. A second family of interneurons, expressing cholecystokinin but not parvalbumin, is known to target the same domains of pyramidal cells as do the parvalbumin cells. To test the temporal activity of these independent and parallel GABAergic inputs, we recorded the precise spike timing of identified cholecystokinin interneurons during hippocampal network oscillations in anesthetized rats and determined their molecular expression profiles and synaptic targets. The cells were cannabinoid receptor type 1 immunopositive. Contrary to the stereotyped firing of parvalbumin interneurons, cholecystokinin-expressing basket and dendrite-innervating cells discharge, on average, with 1.7 Ϯ 2.0 Hz during high-frequency ripple oscillations in an episode-dependent manner. During theta oscillations, cholecystokinin-expressing interneurons fire with 8.8 Ϯ 3.3 Hz at a characteristic time on the ascending phase of theta waves (155 Ϯ 81°), when place cells start firing in freely moving animals. The firing patterns of some interneurons recorded in drug-free behaving rats were similar to cholecystokinin cells in anesthetized animals. Our results demonstrate that cholecystokinin-and parvalbumin-expressing interneurons make different contributions to network oscillations and play distinct roles in different brain states. We suggest that the specific spike timing of cholecystokinin interneurons and their sensitivity to endocannabinoids might contribute to differentiate subgroups of pyramidal cells forming neuronal assemblies, whereas parvalbumin interneurons contribute to synchronizing the entire network.

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The ipsilateral corticocortical connections of the somatosensory fields of the lateral sulcus of macaques were examined with both anterograde and retrograde axonal transport methods. In most cases, the field of interest was identified prior to the injection of the tracer substance by recording neuronal responses to somatic stimulation. The results show that the second somatosensory area (S2) is reciprocally connected with the retroinsular area (Ri), area 7b, and the granular (Ig) and dysgranular (Id) insular fields. Ri is also reciprocally connected with Ig. Previously reported connections were confirmed between S2 and areas 3a, 3b, 1, and 2 and between area 5 and both area 7 and Ri. Moreover, the portions of Ig and Id that receive somatic inputs were shown to project to the amygdaloid complex. Id projects, in addition, to the perirhinal cortex, which supplies input to the hippocampal formation. The corticocortical projections were found to have two distinct laminar patterns of termination. One is characterized by heavy terminations in layers IV and IIIb and the other by heavy terminations in layer I, but no terminations in layers IV and IIIb. These two patterns were typically found to be reciprocally related. The results suggest that somatosensory information is processed by a series of cortical fields, including areas 3a, 3b, 1, 2, 5, 7b, S2, Ig, and Id. These fields have access to the amygdaloid complex and the hippocampal formation. Thus, a ventrally directed tactile processing pathway can be followed from S1 to the temporal lobe limbic structures via relays in S2 and the insula; this corticolimbic pathway may subserve tactile learning and memory.

We observed sharp wave/ripples (SWR) during exploration within brief (<2.4 s) interruptions of or during theta oscillations. CA1 network responses of SWRs occurring during exploration (eSWR) and SWRs detected in waking immobility or sleep were similar. However, neuronal activity during eSWR was location dependent, and eSWR-related firing was stronger inside the place field than outside. The eSPW-related firing increase was stronger than the baseline increase inside compared to outside, suggesting a "supralinear" summation of eSWR and place-selective inputs. Pairs of cells with similar place fields and/or correlated firing during exploration showed stronger coactivation during eSWRs and subsequent sleep-SWRs. Sequential activation of place cells was not required for the reactivation of waking co-firing patterns; cell pairs with symmetrical cross-correlations still showed reactivated waking co-firing patterns during sleep-SWRs. We suggest that place-selective firing during eSWRs facilitates initial associations between cells with similar place fields that enable place-related ensemble patterns to recur during subsequent sleep-SWRs.

The hippocampus is thought to be involved in episodic memory formation by reactivating traces of waking experience during sleep. Indeed, the joint firing of spatially tuned pyramidal cells encoding nearby places recur during sleep. We found that the sleep cofiring of rat CA1 pyramidal cells encoding similar places increased relative to the sleep session before exploration. This cofiring increase depended on the number of times that cells fired together with short latencies (<50 ms) during exploration, and was strongest between cells representing the most visited places. This is indicative of a Hebbian learning rule in which changes in firing associations between cells are determined by the number of waking coincident firing events. In contrast, cells encoding different locations reduced their cofiring in proportion to the number of times that they fired independently. Together these data indicate that reactivated patterns are shaped by both positive and negative changes in cofiring, which are determined by recent behavior.

We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse, and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques that include manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common, and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre-existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain structure.

The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.