Hippocampal Circuit Disruptions Underlying Cognitive Deficits Following Traumatic Brain Injury or Induced Seizures Christopher D Adam

Format:

Book

Thesis/Dissertation

Author/Creator:

Adam, Christopher D., author.

Contributor:

University of Pennsylvania. Neuroscience., degree granting institution.

Language:

English

Subjects (All):

Neurosciences.

Cellular biology.

Cognitive psychology.

0317.

0379.

0633.

Local Subjects:

Neurosciences.

Cellular biology.

Cognitive psychology.

0317.

0379.

0633.

Physical Description:

1 electronic resource (149 pages)

Contained In:

Dissertations Abstracts International 86-07B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2024

Language Note:

English

Summary:

Cognitive deficits are a common consequence of both traumatic brain injury (TBI) and temporal lobe epilepsy (TLE) and are often treatment refractory. Learning and memory impairments are especially common in TBI and TLE and are thought to be driven in part by pathological changes to hippocampal circuits that support these processes. Interestingly, both disorders have some overlapping hippocampal circuit pathologies including regional-specific cell loss, increased neurogenesis, mossy fiber sprouting, interneuron loss and dysfunction, and disruptions to hippocampal afferent inputs all of which may disrupt physiological processes that support learning and memory. Additionally, seizures can be a shared consequence of TBI and TLE and may further exacerbate cognitive deficits. Disentangling how hippocampal circuit pathologies and seizures independently contribute to learning and memory deficits is difficult because circuit pathologies can give rise to seizures, and seizures can induce pathological changes in hippocampal circuits. This body of work attempts to separate these two phenomena and explore i) how behaviorally relevant physiological process in the hippocampus are disrupted in TBI and ii) whether seizures generated by experimentally increasing dentate granule cell (DGC) excitability impair spatial memory. Using laminar electrodes, we found a loss of hippocampal theta and gamma oscillatory power and coupling in a model of TBI likely driven by decreased entrainment of interneurons to these oscillations. We believe these changes contribute to learning and memory deficits following TBI. Additionally, we found that increasing DGC excitability with chemogenetics induced seizures and memory deficits in uninjured, non-epileptic mice, providing support for a specific role of seizures in TLE-associated cognitive deficits in the absence of hippocampal pathologies. Results from these studies show that pathological changes to hippocampal circuits in TBI disrupt physiological processes known to support learning and memory, and that seizures in the absence of pathological circuit disruptions can impair memory. Results from these studies may provide insight into future circuit-based neuromodulation therapies that specifically target TBI or TLE associated cognitive deficits arising from pathological changes to hippocampal circuits or from seizures

Notes:

Source: Dissertations Abstracts International, Volume: 86-07, Section: B.

Advisors: Coulter, Douglas A.; Wolf, John A. Committee members: Contreras, Diego; Dani, John A.; Fuccillo, Marc V.; Marsh, Eric D.

Ph.D. University of Pennsylvania 2024

Local Notes:

School code: 0175

ISBN:

9798302183583

Access Restriction:

Restricted for use by site license