Project 461927

Global signals in dendrites of GABAergic inhibitory interneurons: mechanisms and function

461927

Global signals in dendrites of GABAergic inhibitory interneurons: mechanisms and function

$1,032,750
Project Information
Study Type: Unclear
Research Theme: Biomedical
Institution & Funding
Principal Investigator(s): Topolnik, Lisa Y
Institution: Université Laval
CIHR Institute: Neurosciences, Mental Health and Addiction
Program: Project Grant
Peer Review Committee: Systems & Circuits Neurosciences - A
Competition Year: 2022
Term: 5 yrs 0 mth
Abstract Summary

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 brain structure involved in memory formation and retrieval. 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.

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Keywords
Calcium Dendrite Inhibition Interneuron Plasticity Spatial Learning Synapse Two-Photon Imaging