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Ongoing research

Inhibitory control of hippocampal inhibitory circuits: cell types, neuromodulation and function.

Every important event and every significant life episode is encoded in our brain through a concerted dialogue between several cortical structures, including the hippocampus. The hippocampal circuitry takes a central place in the brain cognitive map, making up the memory orchestra. It is composed of two major neuron types: excitatory principal cells and inhibitory neurons. 

The inhibitory neurons make local and long-range connections with principal cells but also with each other. Intriguingly, a distinct population of inhibitory cells that express vasoactive intestinal polypeptide (VIP) exists in the hippocampus that innervates specifically other inhibitory neurons and, therefore, via selective control over entire hippocampal circuitry, may mediate executive cognitive functions important for learning and memory. These disinhibitory cells are highly heterogeneous, comprising morphologically and molecularly distinct cell types. And it is still unknown how many cell types are positioned at different hippocampal crossroads and what can be their function. 

This project aims to shed light on the diversity of the disinhbibitory neurons, their modulation via subcortical projections and their cellular function. Given that imbalanced circuit inhibition is reported in numerous disorders, such as epilepsy, Alzheimer’s disease, schizophrenia and autism, this research may open up new therapeutic avenues towards prevention and treatment of several devastating pathologies.

Mechanisms of dendritic integration and plasticity in GABAergic inhibitory interneurons.

Dendrites, the tree-like neuronal extensions, receive and analyze information from thousands of synaptic inputs and consume most of the brain energy. Activation of a single synapse on a dendrite may affect the firing behavior of the neuron and, accordingly, its contribution to network activity and cognitive processes. As dendrites of different types of neurons exhibit a remarkable diversity in structure, it is believed that they are fit for neuronal function. Indeed, depending on the neuron type, dendrites have a distinctive mosaic of expression of synaptic receptors, ion channels, and membrane transporters that may shape dendritic input integration in a highly dynamic manner. But how this may happen in different types of neurons or, in other words, what are the cell type-specific mechanisms responsible for the functional specialization of dendrites, remains largely unknown. 

This project aims to establish the functional organization of dendrites in two types of interneurons residing in the hippocampus, the parvalbumin- and somatostatin-expressing cells. These cells receive specific excitatory inputs; contribute to the formation of memory engrams but fail in several human neurological and neuropsychiatric disorders including epilepsy, Alzheimer’s disease, schizophrenia, depression, and attention deficit hyperactivity disorder. 

We will examine (1) how dendrites of interneurons may exhibit global activity patterns associated with exploration; (2) how these dendritic patterns can lead to changes in synaptic strength; and (3) how they may control the cell firing during memory formation in awake animals.

 The results of this study will reveal the cell type-specific mechanisms of dendritic signaling and their role during memory encoding in behaving animals. Ultimately, this research will fill the gap between neuronal diversity, function and animal behavior, which is essential for our understanding of how the brain works.