Contributions Of Ca1 Inhibitory Interneurons To Cerebello-Hippocampal Communication
2024-04
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Contributions Of Ca1 Inhibitory Interneurons To Cerebello-Hippocampal Communication
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2024-04
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The cerebellum is classically considered a motor structure, but the “little brain” is now being much more widely accepted for its roles in cognition, both in its own right and via communications with other brain regions like the hippocampus (a brain region chiefly known for its roles in learning, memory and spatial processing). Our lab terms the bidirectional connectivity between these two regions the ‘hippobellum’. The two structures interact in both healthy brains and in pathological states such as in Temporal Lobe Epilepsy. The focus of this dissertation is to assess the contributions of inhibitory cells within hippocampal CA1 to cerebello-hippocampal communication. We find that the cerebellum bidirectionally affects interneurons, increasing activity in some while decreasing activity in others. We also found some interneurons are modulated during object exploration. Highlighting the coordination between the cerebellum and the hippocampus in spatial processing, interneurons modulated during object investigations are also modulated by cerebellar stimulation. We also characterized interneurons in accordance with their activity during locomotion and rest; a subset of these neurons, too, are modulated by cerebellar stimulation. Our functional characterizations revealed specific patterns of interneuron responses to cerebellar stimulation: interneurons that increased their activity with cerebellar stimulation also tended to increase their activity with locomotion and during object investigations. Conversely, interneurons that decreased their activity with cerebellar stimulation tended to be more active during rest and also decreased their activity during object investigations. Similar results were found using different stimulation parameters within the cerebellum and when stimulating a different cerebellar location, showing multiple ways the cerebellum can influence hippocampal interneurons and that it can do so in a bidirectional, coordinated fashion – according to the roles of those interneurons during behavior. In another experiment, we used common molecular markers of interneurons in conjunction with cFOS (a proxy for neuronal activity) to label hippocampal neurons activated by cerebellar stimulation ex vivo. We found that cerebellar stimulation increases cFOS expression in both CCK-expressing and SOM-expressing cells in hippocampal CA1. Overall. our results support the notion that CA1 inhibitory neurons play a role in cerebello-hippocampal interactions and prompt exciting new directions in this field.
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University of Minnesota Ph.D. dissertation. April 2024. Major: Neuroscience. Advisor: Esther Krook-Magnuson. 1 computer file (PDF); xiii, 160 pages.
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