Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


Thesis_HLRobinson_GS_edits.pdf (11.37 MB)

ETD Abstract Container

Abstract Header

ERBB4 KINASE DYNAMICALLY REGULATES HIPPOCAMPAL-PREFRONTAL SYNCHRONY AND HIPPOCAMPAL SHARP WAVE RIPPLES IMPORTANT FOR ATTENTION AND MEMORY

Robinson, Heath Larsson
http://rave.ohiolink.edu/etdc/view?acc_num=case1643711448048167

Abstract Details

2022, Doctor of Philosophy, Case Western Reserve University, Neurosciences.
Neurotrophic factors are released in the brain in response to neural activity. In so doing, they can modulate neuronal circuits. Yet how exactly neurotrophic factors impact networks of the brain and by what underlying mechanisms are just becoming understood. Neuregulin 1 (NRG1) is one such trophic factor that is released in the brain upon neuronal activity. NRG1 binds to and stimulates the receptor tyrosine kinase (RTK) ErbB4 that is expressed in inhibitory interneurons. Stimulation of ErbB4 kinase then increases Gamma-Aminobutyric Acid (GABA) neurotransmission in the cortex and HPC. Yet how ErbB4 kinase dynamically impacts the cortex, HPC, and relevant behaviors remains unknown. By developing a novel chemo-genetic animal model to specifically manipulate ErbB4 kinase, we identify two distinct network functions of the brain that ErbB4 kinase regulates, along with relevant behaviors involved in these network functions. First, we identify a novel behavioral function for the ventral HPC (vHPC) to prefrontal cortex (PFC) circuit. We find that the vHPC-PFC is highly synchronous during top-down attention. We next identify how ErbB4 plays a role in top-down attention, by regulating vHPC-PFC synchronicity. We further validate that ErbB4 kinase dynamically regulates GABAergic transmission via presynaptic xviii modulation. Lastly, we identify how ErbB4, via regulation of GABAergic transmission, controls vHPC-PFC synchrony through vHPC inputs to the PFC that lead PFC neurons to fire in phase. Together, we identify how ErbB4 kinase dynamically regulates the synchrony between two regions for top-down attention. Next, we examine how NRG1-ErbB4 kinase regulates a memory consolidation network event in the HPC called the sharp wave ripple (SW-R). Specifically, we find that NRG1-ErbB4 kinase dynamically regulate the occurrence of SW-Rs, especially during awake periods. Furthermore, we uncover that ErbB4 kinase regulates levels of neuronal firing, specifically pyramidal neurons (PyNs), as well as PyN dynamics during SW-R events. Lastly, by taking advantage of a continuous spatial working memory task adapted for mice, we identify that ErbB4 kinase dynamically regulates spatial working memory. In conclusion, we discover how NRG1-ErbB4 kinase regulate the occurrence of an important memory event in the HPC, the SW-R, as well how ErbB4 kinase dynamically regulates spatial working memory.
Lin Mei, Dr. (Advisor)
Ben Strowbridge, Dr. (Committee Chair)
Qian Sun, Dr. (Committee Member)
Dominique Durand, Dr. (Committee Member)
Heather Broihier, Dr. (Committee Member)
318 p.
Neurobiology; Neurosciences
Memory, Neuroscience, Sharp Wave Ripples, Synchrony, Hippocampus, Prefrontal Cortex, Phase Locking, Attention, Erbb4, Neuregulin 1

Recommended Citations

Citations

  • Robinson, H. L. (2022). ERBB4 KINASE DYNAMICALLY REGULATES HIPPOCAMPAL-PREFRONTAL SYNCHRONY AND HIPPOCAMPAL SHARP WAVE RIPPLES IMPORTANT FOR ATTENTION AND MEMORY [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1643711448048167

    APA Style (7th edition)

  • Robinson, Heath. ERBB4 KINASE DYNAMICALLY REGULATES HIPPOCAMPAL-PREFRONTAL SYNCHRONY AND HIPPOCAMPAL SHARP WAVE RIPPLES IMPORTANT FOR ATTENTION AND MEMORY. 2022. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1643711448048167.

    MLA Style (8th edition)

  • Robinson, Heath. "ERBB4 KINASE DYNAMICALLY REGULATES HIPPOCAMPAL-PREFRONTAL SYNCHRONY AND HIPPOCAMPAL SHARP WAVE RIPPLES IMPORTANT FOR ATTENTION AND MEMORY." Doctoral dissertation, Case Western Reserve University, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=case1643711448048167

    Chicago Manual of Style (17th edition)

case1643711448048167
148
© 2022, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.