monitoring-fine-associative-motor-learning-mice-using-erasmus

Monitoring Fine and Associative Motor Learning in Mice Using the Erasmus Ladder

Behavior is shaped by actions, and actions necessitate motor skills such as strength, coordination, and learning. None of the behaviors essential for ...

Spain - Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández

Recent results suggest that social memory requires the dorsal hippocampal CA2 region as well as a subset of ventral CA1 neurons. However, it is unclear whether dorsal CA2 and ventral CA1 represent parallel or sequential circuits. Moreover, because evidence implicating CA2 in social memory comes largely from long-term inactivation experiments, the dynamic role of CA2 in social memory remains unclear. Here, we use pharmacogenetics and optogenetics in mice to acutely and reversibly silence dorsal CA2 and its projections to ventral hippocampus. We show that dorsal CA2 activity is critical for encoding, consolidation, and recall phases of social memory. Moreover, dorsal CA2 contributes to social memory by providing strong excitatory input to the same subregion of ventral CA1 that contains the subset of neurons implicated in social memory. Thus, our studies provide new insights into a dorsal CA2 to ventral CA1 circuit whose dynamic activity is necessary for social memory.

A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics.

Over the past half-century, we have gained significant insights into the molecular biology of long-term memory storage at the level of the synapse. In recent years, our understanding of the cellular architecture supporting long-term memory traces has also substantially improved. However, the molecular biology of consolidation at the level of neuronal systems has been relatively neglected. In this opinion article, we first examine our current understanding of the cellular mechanisms of synaptic consolidation. We then outline areas requiring further investigation on how cellular changes contribute to systems consolidation. Finally, we highlight recent findings on the cellular architecture of memory traces in rodents and how the application of new technologies will expand our understanding of systems consolidation at the neural circuit level. In the coming years, this research focus will be critical for understanding the evolution of long-term memories and for enabling the development of novel therapeutics which embrace the dynamic nature of memories.

Molecular Mechanisms of the Memory Trace.

Although the hippocampus is known to be important for declarative memory, it is less clear how hippocampal output regulates motivated behaviours, such as social aggression. Here we report that pyramidal neurons in the CA2 region of the hippocampus, which are important for social memory, promote social aggression in mice. This action depends on output from CA2 to the lateral septum, which is selectively enhanced immediately before an attack. Activation of the lateral septum by CA2 recruits a circuit that disinhibits a subnucleus of the ventromedial hypothalamus that is known to trigger attack. The social hormone arginine vasopressin enhances social aggression by acting on arginine vasopressin 1b receptors on CA2 presynaptic terminals in the lateral septum to facilitate excitatory synaptic transmission. In this manner, release of arginine vasopressin in the lateral septum, driven by an animal's internal state, may serve as a modulatory control that determines whether CA2 activity leads to declarative memory of a social encounter and/or promotes motivated social aggression.

A circuit from hippocampal CA2 to lateral septum disinhibits social aggression.

How does cognition regulate innate behaviors? While the cognitive functions of the cortex have been extensively studied, we know much less about how cognition can regulate innate motivated behaviors to fulfill physiological, safety and social needs. Selection of appropriate motivated behaviors depends on external stimuli and past experiences that helps to scale priorities. With its abundant inputs from neocortical and allocortical regions, the lateral septum (LS) is ideally positioned to integrate perception and experience signals in order to regulate the activity of hypothalamic and midbrain nuclei that control motivated behaviors. In addition, LS receives numerous subcortical modulatory inputs, which represent the animal internal states and also participate in this regulation. In this perspective, we argue that LS sub-circuits regulate distinct motivated behaviors by integrating neural activity from neocortical, allocortical and neuromodulatory inputs. In addition, we propose that lateral inhibition between LS sub-circuits may allow the emergence of functional units that orchestrates competing motivated behaviors.

Article	Year
A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics. Nature communications\| PubMed ID: 30301899
Molecular Mechanisms of the Memory Trace. Trends in neurosciences\| PubMed ID: 30391015
A circuit from hippocampal CA2 to lateral septum disinhibits social aggression. Nature\| PubMed ID: 30518859
Top-down regulation of motivated behaviors via lateral septum sub-circuits. Molecular psychiatry\| PubMed ID: 35581296	2022

Felix Leroy

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