Encoding and retrieval in a CA1 microcircuit model of the hippocampus

Recent years have witnessed a dramatic accumulation of knowledge about the morphological, physiological and molecular characteristics, as well as connectivity and synaptic properties of neurons in the mammalian hippocampus. Despite these advances, very little insight has been gained into the computational function of the different neuronal classes; in particular, the role of the various inhibitory interneurons in encoding and retrieval of information remains elusive. Mathematical and computational models of microcircuits play an instrumental role in exploring microcircuit functions and facilitate the dissection of operations performed by diverse inhibitory interneurons. A model of the CA1 microcircuitry is presented using biophysical representations of its major cell types: pyramidal, basket, axo-axonic, bistratified and oriens lacunosummoleculare cells. Computer simulations explore the biophysical mechanisms by which encoding and retrieval of spatio-temporal input patterns are achieved by the CA1 microcircuitry. The model proposes functional roles for the different classes of inhibitory interneurons in the encoding and retrieval cycles

Long-term suppression of forebrain neurogenesis and loss of neuronal progenitor cells following prolonged alcohol dependence in rats.

Alcohol dependence leads to persistent neuroadaptations, potentially related to structural plasticity. Previous work has shown that hippocampal neurogenesis is modulated by alcohol, but effects of chronic alcohol on neurogenesis in the forebrain subventricular zone (SVZ) have not been reported. Effects in this region may be relevant for the impairments in olfactory discrimination present in alcoholism. Here, we examined the effects of prolonged alcohol dependence on neurogenesis. Rats were sacrificed directly after 7 wk of intermittent alcohol vapour exposure, or 3, 7 or 21 d into abstinence. Proliferation was assessed using BrdU and Ki67 immunoreactivity, newly differentiated neurons (neurogenesis) as doublecortin-immunoreactivity (DCX-IR), and neural stem cells using the SOX2 marker. In the dentate gyrus, chronic dependence resulted in a pattern similar to that previously reported for acute alcohol exposure: proliferation and neurogenesis were suppressed by the end of exposure, rebounded on day 3 of abstinence, and returned to control levels by days 7 and 21. In the SVZ, proliferation was also suppressed at the end of alcohol exposure, followed by a proliferation burst 3 d into abstinence. However, in this area, there was a trend for reduced proliferation on days 7 and 21 of abstinence, and this was accompanied by significant suppression of DCX-IR, indicating a long-term suppression of forebrain neurogenesis. Finally, a decrease in the SOX2 stem cell marker was detected at days 7 and 21, suggesting long-term reduction of the SVZ stem cell pool. While suppression of hippocampal neurogenesis by alcohol dependence is transient, the suppression in the forebrain SVZ appears long-lasting

LONG-LASTING SUPPRESSION OF SUBVENTRICULAR ZONE NEUROGENESIS FOLLOWING A HISTORY OF ETHANOL DEPENDENCE

Exposure to repeated cycles of ethanol intoxication and withdrawal results in a well characterized persistent post-dependent increase in excessive voluntary ethanol consumption and behavioral sensitivity to stress. We have previously described some molecular neuroadaptations that contribute to these behavioral traits. Formation of new neurons in the adult brain, or adult neurogenesis, is related to stress responsiveness, and previous work has established that it is modulated by ethanol intoxication and withdrawal. Here, we asked whether adult neurogenesis is altered in the post-dependent state, in a manner that could contribute to the functional phenotype observed in this condition. To this end, we studied cell proliferation and neurogenesis in the subgranular zone of the dentate gyrus (SGZ) and in the subventricular zone lining the lateral ventricle (SVZ) in rats over a period of 3 weeks following a previously described 7 week intermittent ethanol vapor exposure to induce dependence, and compared to controls without a history of ethanol exposure. A single dose of 5-bromo-2-deoxyuridine (BrdU, 200 mg/kg, i.p.) was administered 4-5 h prior to euthanasia on day 0, 3, 7 and 21 post induction of dependence (abstinence days). Proliferating precursor cells incorporate the mitotic marker BrdU and were identified using immunohistochemistry in SVZ and SGZ. In agreement with prior work, ethanol exposure decreased density and number of proliferating cells by 70 % in both the SVZ (p<0.001) and SGZ (p<0.05), followed by a 2- fold rebound burst in proliferation on day 3 (p<0.001) of abstinence. In the SGZ, proliferation returned to normal levels within one week. However, the density of proliferating cells in the SVZ remained significantly decreased on day 7 (36%, p<0.01) and day 21 (35%, p<0.05) of abstinence. These changes were paralleled by decreased doublecortin expression, a neuronal marker expressed shortly after neuronal cell fate determination. Our data indicate a long-lasting suppression of neurogenesis in the SVZ of post-dependent rats, potentially leading to reduced neuronal turnover in the olfactory bulb and possibly also in prefrontal cortex circuitry. Although, the functional correlates of SVZ suppression are unknown, loss of olfactory discrimination is common in alcoholics and correlates with loss of executive function

Spiking Associative Memory and Scene Segmentation by Synchronization of Cortical Activity

For the recognition of objects there are a number of computational requirements that go beyond the detection of simple geometric features like oriented lines. When there are several partially occluded objects present in a visual scene one has to have an internal knowledge about the object to be identified, e.g. using associative memories