hybrid-microdrive-system-with-recoverable-opto-silicon-probe-tetrode

Hybrid Microdrive System with Recoverable Opto-Silicon Probe and Tetrode for Dual-Site High Density Recording in Freely Moving Mice

Multi-regional neural recordings can provide crucial information to understanding fine-timescale interactions between multiple brain regions. However, ...

University of Texas Southwestern Medical Center

Episodic memories shape future behaviour and by aiding adaptive behaviour, are therefore important for survival in nature. Entorhinal cortex (EC)-hippocampal (HPC) networks have a crucial role in the formation of episodic memory, which consists of associations of space, objects, individuals and time. Neural circuits have been identified in the EC-HPC networks that provide spatial, contextual and object information. However, the specific neural circuits that allow animals to associate two temporally segregated events, called temporal association learning, are still nebulous. In this review, I will review recent experimental evidence concerning the role of the EC in temporal association learning, with an emphasis on the neural circuits functioning to drive and regulate the temporal associations between events, and focusing on the trace fear conditioning paradigm in rodents. Then, I will discuss hippocampal activity during the trace periods that may bridge the temporal gap in memory for discontinuous events. Finally, I examine the role of the prefrontal cortex as a central executive system to track and extract predictive relationships between events by the coordination of the EC-HPC network.

Driving and regulating temporal association learning coordinated by entorhinal-hippocampal network.

What happens to memories as days, weeks and years go by has long been a fundamental question in neuroscience and psychology. For decades, researchers have attempted to identify the brain regions in which memory is formed and to follow its changes across time. The theory of systems consolidation of memory (SCM) suggests that changes in circuitry and brain networks are required for the maintenance of a memory with time. Various mechanisms by which such changes may take place have been hypothesized. Recently, several studies have provided insight into the brain networks driving SCM through the characterization of memory engram cells, their biochemical and physiological changes and the circuits in which they operate. In this Review, we place these findings in the context of the field and describe how they have led to a revamped understanding of SCM in the brain.

The role of engram cells in the systems consolidation of memory.

The hippocampus is crucial for declarative memories in humans and encodes episodic and spatial memories in animals. Memory coding strengthens synaptic efficacy via an LTP-like mechanism. Given that animals store memories of everyday experiences, the hippocampal circuit must have a mechanism that prevents saturation of overall synaptic weight for the preservation of learning capacity. LTD works to balance plasticity and prevent saturation. In addition, adult neurogenesis in the hippocampus is proposed to be involved in the down-scaling of synaptic efficacy. Here, we show that adult neurogenesis in male rats plays a crucial role in the maintenance of hippocampal capacity for memory (learning and/or memory formation). Neurogenesis regulated the maintenance of LTP, with decreases and increases in neurogenesis prolonging or shortening LTP persistence, respectively. Artificial saturation of hippocampal LTP impaired memory capacity in contextual fear conditioning, which completely recovered after 14 d, which was the time required for LTP to decay to the basal level. Memory capacity gradually recovered in parallel with neurogenesis-mediated gradual decay of LTP. Ablation of neurogenesis by x-ray irradiation delayed the recovery of memory capacity, whereas enhancement of neurogenesis using a running wheel sped up recovery. Therefore, one benefit of ongoing adult neurogenesis is the maintenance of hippocampal memory capacity through homeostatic renewing of hippocampal memory circuits. Decreased neurogenesis in aged animals may be responsible for the decline in cognitive function with age. Learning many events each day increases synaptic efficacy via LTP, which can prevent the storage of new memories in the hippocampal circuit. In this study, we demonstrate that hippocampal capacity for the storage of new memories is maintained by ongoing adult neurogenesis through homoeostatic renewing of hippocampal circuits in rats. A decrease or an increase in neurogenesis, respectively, delayed or sped up the recovery of memory capacity, suggesting that hippocampal adult neurogenesis plays a critical role in reducing LTP saturation and keeps the gate open for new memories by clearing out the old memories from the hippocampal memory circuit.

Adult Neurogenesis Conserves Hippocampal Memory Capacity.

The brain stores and recalls memories through a set of neurons, termed engram cells. However, it is unclear how these cells are organized to constitute a corresponding memory trace. We established a unique imaging system that combines Ca imaging and engram identification to extract the characteristics of engram activity by visualizing and discriminating between engram and non-engram cells. Here, we show that engram cells detected in the hippocampus display higher repetitive activity than non-engram cells during novel context learning. The total activity pattern of the engram cells during learning is stable across post-learning memory processing. Within a single engram population, we detected several sub-ensembles composed of neurons collectively activated during learning. Some sub-ensembles preferentially reappear during post-learning sleep, and these replayed sub-ensembles are more likely to be reactivated during retrieval. These results indicate that sub-ensembles represent distinct pieces of information, which are then orchestrated to constitute an entire memory.

Orchestrated ensemble activities constitute a hippocampal memory engram.

The hippocampus (HPC) is required for the initial process of permanent memory formation. After memory acquisition, HPC-dependency of memory recall gradually decreases with time, whereas cortical-dependency of memory recall increases. This phenomenon is often referred to as systems consolidation of memory. In the HPC, adult neurogenesis has been described in many mammalian species and is involved in the process of learning and memory. In this review, we first examine the neural circuit mechanisms that underlie the systems consolidation of episodic memories, focusing on adult neurogenesis within the HPC. Recently, several studies have examined the characterization of memory engram cells, their biochemical and physiological changes, and the circuits for systems consolidation of memory. Therefore, we discuss the possible role of adult neurogenesis on functional states of memory engram cells, and speculate the implications of this transition of memory type for psychiatric disorders such as post-traumatic stress disorder.

Article	Year
Driving and regulating temporal association learning coordinated by entorhinal-hippocampal network. Neuroscience research\| PubMed ID: 28483587	2017
The role of engram cells in the systems consolidation of memory. Nature reviews. Neuroscience\| PubMed ID: 29970909	2018
Adult Neurogenesis Conserves Hippocampal Memory Capacity. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 29986876	2018
Orchestrated ensemble activities constitute a hippocampal memory engram. Nature communications\| PubMed ID: 31201332	2019
Adult hippocampal neurogenesis for systems consolidation of memory. Behavioural brain research\| PubMed ID: 31201874	2019

Takashi Kitamura

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