Revealing the role of hippocampal interneurons and principal cells in navigation and planning
Description: GABAergic interneurons of the hippocampus, the learning and memory center of the brain, are known to play critical roles in normal cognitive functions such as learning and memory. Interneurons make up approximately 10% of the whole neuronal population of the hippocampus but modulate the activity of several thousand principal cells. Thus, interneurons can be considered hub neurons that can play as a central switch for gating memory function. However, determining their physiological role in cognitive function has been difficult to determine because they are very sparse, and electrophysiological recordings are challenging. However, experimental tools recently developed such as miniature microscopy using miniscopes in combination with calcium imaging now offers a unique opportunity to determine how different types of interneurons behave in cognitive tasks in freely behaving mice. We have focused on a type of interneuron located in the oriens-alveus layer and axons in the lacunosum-moleculare (OLM) that are suggested to control the CA3 input and the entorhinal cortex input. Since CA3 and EC input is thought to support retrieval and encoding, respectively, OLM interneurons are likely very important for normal memory function. We use a combination of techniques together with calcium imaging including DREADDs and optogenetics to silence OLM activity at key moments during the tasks. We hypothesize that OLM interneurons play a role in navigation, prediction, and goal-directed planning. In addition, one of the primary inhibitory inputs to OLM interneurons, originating from VIP interneurons display different roles than OLM interneurons. Finally, we also show data that OLM interneuron activity is disrupted in aging and in Alzheimer's mouse models. Our proposal, provide unique data suggesting that OLM interneurons are key players underlying navigation and memory encoding and recall.
Amount: CA$975,400
Funding type: research
Funder scheme: Project Grant
Start date: 2023-07-01
End date: 2028-06-30
Investigator: Sylvain Williams
Institution: Douglas Mental Health University Institute (Montreal, QC)
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Funded outputs count: 0
Funder award ID: 186113_1
OpenAlex ID: G3754916674