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Contributions of CA1 Inhibitory Interneurons to Cerebello-Hippocampal Communication.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Contributions of CA1 Inhibitory Interneurons to Cerebello-Hippocampal Communication./
Author:	Froula, Jessica Marie.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2024,
Description:	176 p.
Notes:	Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
Contained By:	Dissertations Abstracts International85-11B.
Subject:	Neurosciences. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31241422
ISBN:	9798382721682

Contributions of CA1 Inhibitory Interneurons to Cerebello-Hippocampal Communication.
Froula, Jessica Marie.

Contributions of CA1 Inhibitory Interneurons to Cerebello-Hippocampal Communication. - Ann Arbor : ProQuest Dissertations & Theses, 2024 - 176 p.

Source: Dissertations Abstracts International, Volume: 85-11, Section: B.

Thesis (Ph.D.)--University of Minnesota, 2024.

The cerebellum is classically considered a motor structure, but the "little brain", which contains over 50% of the brain's neurons, contributes much more to brain function than precise timing and coordination of movements. It is now being much more widely accepted for its roles in cognition, both in its own right and via communications with other brain regions. One major structure the cerebellum interacts with to support cognition is 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 the context of Temporal Lobe Epilepsy. The focus of this dissertation is to assess the contributions of inhibitory cells within hippocampal CA1 to cerebello-hippocampal communication.In Chapter 1, I present a review of current literature about the Hippobellum. The two structures support each other with functions such as timing, coordinated oscillations in different brain states (including during sleep), and in spatial processing. Anatomical pathways between the two regions have not been fully characterized, but it is clear that the connection, though powerful, is not direct. The field studying Hippobellum interactions is relatively new, filled with rich and exciting possible future directions.In Chapter 2, we zoom in on the hippocampus to assess the effects of cerebellar modulation on inhibitory circuitry within the CA1 subregion. Specifically, we use calcium imaging in combination with optogenetics to activate cerebellar Purkinje cells while imaging CA1 inhibitory interneurons. We find that the cerebellum bidirectionally affects interneurons, increasing activity in some while decreasing activity in others. We also found a population of interneurons that is modulated during object exploration. Highlighting the coordination between the cerebellum and the hippocampus in spatial processing, interneurons that are modulated during object investigations are also modulated by cerebellar stimulation. We also characterized interneurons in accordance with their activity{A0}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 when using different stimulation parameters within the cerebellum and when stimulating a different location in the cerebellum, supporting prior work showing multiple ways the cerebellum can influence the hippocampus. This study shows that not only is the cerebellum able to impact hippocampal interneurons, but it does so in a bidirectional, coordinated fashion according to the roles of those interneurons during behavior.In Chapter 3, we again take a single cell level approach to study how the cerebellum impacts hippocampal interneurons. Rather than the functional characterizations used in Chapter 2, we used common molecular markers of interneurons in conjunction with cFOS (a proxy for neuronal activity) to label hippocampal neurons activated by cerebellar stimulation. We found that cerebellar stimulation increases cFOS expression in both CCK-expressing and SOM-expressing cells in hippocampal CA1. Conversely, PV+ interneurons' expression of cFOS appears to be unaffected by cerebellar stimulation. Taken together with our calcium imaging results, they support the finding that multiple types of interneurons are impacted by cerebellar stimulation and provide additional context for the molecular profiles of those cells.Chapter 4 discusses the research on the Hippobellum with regards to Temporal Lobe Epilepsy (TLE) and how the current research may fit into our understanding of the cerebellum's effectiveness at reducing seizure burden. The cerebellum had been previously considered a potential therapeutic target for different types of epilepsies but fell out of favor due to inconsistent methodologies and mixed results from clinical studies. More recent studies, including several from colleagues in this lab, have shown that there is hope for the cerebellum as a target in epilepsy, particularly with regards to TLE. It is important to note that the studies in this dissertation were conducted in healthy, non-epileptic mice and therefore have limited direct insights into the Hippobellum functionality in the pathological brain state of TLE. However, understanding the ways that the cerebellum communicates with specific hippocampal cell populations in healthy brains, particularly with regard to inhibitory cell types, can still be informative to this line of work.The goal of the major experiments in this dissertation was to understand the impact that the cerebellum has on inhibitory circuits within the hippocampus. Our results support a role of CA1 inhibitory neurons in cerebello-hippocampal interactions and prompt exciting new directions in this field of study.

ISBN: 9798382721682Subjects--Topical Terms:

588700
Neurosciences.
Subjects--Index Terms:

Cerebellum

Contributions of CA1 Inhibitory Interneurons to Cerebello-Hippocampal Communication.
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520 $a The cerebellum is classically considered a motor structure, but the "little brain", which contains over 50% of the brain's neurons, contributes much more to brain function than precise timing and coordination of movements. It is now being much more widely accepted for its roles in cognition, both in its own right and via communications with other brain regions. One major structure the cerebellum interacts with to support cognition is 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 the context of Temporal Lobe Epilepsy. The focus of this dissertation is to assess the contributions of inhibitory cells within hippocampal CA1 to cerebello-hippocampal communication.In Chapter 1, I present a review of current literature about the Hippobellum. The two structures support each other with functions such as timing, coordinated oscillations in different brain states (including during sleep), and in spatial processing. Anatomical pathways between the two regions have not been fully characterized, but it is clear that the connection, though powerful, is not direct. The field studying Hippobellum interactions is relatively new, filled with rich and exciting possible future directions.In Chapter 2, we zoom in on the hippocampus to assess the effects of cerebellar modulation on inhibitory circuitry within the CA1 subregion. Specifically, we use calcium imaging in combination with optogenetics to activate cerebellar Purkinje cells while imaging CA1 inhibitory interneurons. We find that the cerebellum bidirectionally affects interneurons, increasing activity in some while decreasing activity in others. We also found a population of interneurons that is modulated during object exploration. Highlighting the coordination between the cerebellum and the hippocampus in spatial processing, interneurons that are modulated during object investigations are also modulated by cerebellar stimulation. We also characterized interneurons in accordance with their activity{A0}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 when using different stimulation parameters within the cerebellum and when stimulating a different location in the cerebellum, supporting prior work showing multiple ways the cerebellum can influence the hippocampus. This study shows that not only is the cerebellum able to impact hippocampal interneurons, but it does so in a bidirectional, coordinated fashion according to the roles of those interneurons during behavior.In Chapter 3, we again take a single cell level approach to study how the cerebellum impacts hippocampal interneurons. Rather than the functional characterizations used in Chapter 2, we used common molecular markers of interneurons in conjunction with cFOS (a proxy for neuronal activity) to label hippocampal neurons activated by cerebellar stimulation. We found that cerebellar stimulation increases cFOS expression in both CCK-expressing and SOM-expressing cells in hippocampal CA1. Conversely, PV+ interneurons' expression of cFOS appears to be unaffected by cerebellar stimulation. Taken together with our calcium imaging results, they support the finding that multiple types of interneurons are impacted by cerebellar stimulation and provide additional context for the molecular profiles of those cells.Chapter 4 discusses the research on the Hippobellum with regards to Temporal Lobe Epilepsy (TLE) and how the current research may fit into our understanding of the cerebellum's effectiveness at reducing seizure burden. The cerebellum had been previously considered a potential therapeutic target for different types of epilepsies but fell out of favor due to inconsistent methodologies and mixed results from clinical studies. More recent studies, including several from colleagues in this lab, have shown that there is hope for the cerebellum as a target in epilepsy, particularly with regards to TLE. It is important to note that the studies in this dissertation were conducted in healthy, non-epileptic mice and therefore have limited direct insights into the Hippobellum functionality in the pathological brain state of TLE. However, understanding the ways that the cerebellum communicates with specific hippocampal cell populations in healthy brains, particularly with regard to inhibitory cell types, can still be informative to this line of work.The goal of the major experiments in this dissertation was to understand the impact that the cerebellum has on inhibitory circuits within the hippocampus. Our results support a role of CA1 inhibitory neurons in cerebello-hippocampal interactions and prompt exciting new directions in this field of study.
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