中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior

Adult hippocampal neurogenesis has been implicated in cognitive processes, such as pattern separation, and in the behavioural effects of stress and antidepressants. Young adult-born neurons have been shown to inhibit the overall activity of the dentate gyrus by recruiting local interneurons, which may result in sparse contextual representations and improved pattern separation. We propose that neurogenesis-mediated inhibition also reduces memory interference and enables reversal learning both in neutral situations and in emotionally charged ones. Such improved cognitive flexibility may in turn help to decrease anxiety-like and depressive-like behaviour.

/pdf/adult-hippocampal-neurogenesis-and-cognitive-flexibility-36h50mb7qw.pdf

Adult hippocampal neurogenesis and cognitive flexibility - linking memory and mood.

Recent studies have revealed the existence of hippocampal neurons that fire at successive moments in temporally structured experiences. Several studies have shown that such temporal coding is not attributable to external events, specific behaviours or spatial dimensions of an experience. Instead, these cells represent the flow of time in specific memories and have therefore been dubbed 'time cells'. The firing properties of time cells parallel those of hippocampal place cells; time cells thus provide an additional dimension that is integrated with spatial mapping. The robust representation of both time and space in the hippocampus suggests a fundamental mechanism for organizing the elements of experience into coherent memories.

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Time cells in the hippocampus: a new dimension for mapping memories

The hippocampus as a cognitive map

Intelligent behavior demands coordination among the multiple forms of spatial representation generated in distinct neural structures. Here, Alexander and Nitz show that retrosplenial cortex neuron ensembles conjunctively encode progression through routes, environmental position, and the actions of the animal. Thus, the region may serve as a critical interface between brain regions generating different forms of spatial mapping.

Retrosplenial cortex maps the conjunction of internal and external spaces

Spatially Periodic Activation Patterns of Retrosplenial Cortex Encode Route Sub-spaces and Distance Traveled.

The retrosplenial cortex is reciprocally connected with multiple structures implicated in spatial cognition, and damage to the region itself produces numerous spatial impairments. Here, we sought to characterize spatial correlates of neurons within the region during free exploration in two-dimensional environments. We report that a large percentage of retrosplenial cortex neurons have spatial receptive fields that are active when environmental boundaries are positioned at a specific orientation and distance relative to the animal itself. We demonstrate that this vector-based location signal is encoded in egocentric coordinates, is localized to the dysgranular retrosplenial subregion, is independent of self-motion, and is context invariant. Further, we identify a subpopulation of neurons with this response property that are synchronized with the hippocampal theta oscillation. Accordingly, the current work identifies a robust egocentric spatial code in retrosplenial cortex that can facilitate spatial coordinate system transformations and support the anchoring, generation, and utilization of allocentric representations.

Egocentric boundary vector tuning of the retrosplenial cortex.

A recent model of the hippocampus predicts that the unique properties of the dentate gyrus allow for temporal separation of events. This temporal separation is accomplished in part through the continual generation of new neurons, which, due to a transient window of hyperexcitability, could allow for preferential encoding of information present during their development. Here we obtain in vivo electrophysiological recordings and identify a cell population exhibiting activity that is selective to single contexts when rats experience a long temporal separation between context exposures during training. This selectivity is attenuated as the temporal separation between context exposures is shortened and is further attenuated when neurogenesis is reduced. Our data reveal the existence of a temporal orthogonalizing neuronal code within the dentate gyrus, a hallmark feature of episodic memory.

/pdf/temporally-selective-contextual-encoding-in-the-dentate-3nsyh92grh.pdf

Temporally selective contextual encoding in the dentate gyrus of the hippocampus

The retrosplenial cortex is reciprocally connected with a majority of structures implicated in spatial cognition and damage to the region itself produces numerous spatial impairments. However, in many ways the retrosplenial cortex remains understudied. Here, we sought to characterize spatial correlates of neurons within the region during free exploration in two-dimensional environments. We report that a large percentage of retrosplenial cortex neurons have spatial receptive fields that are active when environmental boundaries are positioned at a specific orientation and distance relative to the animal itself. We demonstrate that this vector-based location signal is encoded in egocentric coordinates, localized to the dysgranular retrosplenial sub-region, independent of self-motion, and context invariant. Further, we identify a sub-population of neurons with this response property that are synchronized with the hippocampal theta oscillation. Accordingly, the current work identifies a robust egocentric spatial code in retrosplenial cortex that can facilitate spatial coordinate system transformations and support the anchoring, generation, and utilization of allocentric representations.

https://www.biorxiv.org/content/biorxiv/early/2019/07/15/702712.full.pdf

Andrew S. Alexander

Papers

Retrosplenial cortex maps the conjunction of internal and external spaces

Spatially Periodic Activation Patterns of Retrosplenial Cortex Encode Route Sub-spaces and Distance Traveled.

Egocentric boundary vector tuning of the retrosplenial cortex.

Temporally selective contextual encoding in the dentate gyrus of the hippocampus

Egocentric boundary vector tuning of the retrosplenial cortex