The Role of Prefrontal-Hippocampal Circuit in the Memory for Sequences of Events

Authors

Maanasa N. JayachandranFollow

Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Cognitive Neuroscience

First Advisor's Name

Dr. Timothy A. Allen

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Dr. Aaron Mattfeld

Second Advisor's Committee Title

Committee Member

Third Advisor's Name

Dr. Robert Lickliter

Third Advisor's Committee Title

Committee Member

Fourth Advisor's Name

Dr. Kim Tieu

Fourth Advisor's Committee Title

Committee Member

Fifth Advisor's Name

Dr. Robert P. Vertes

Fifth Advisor's Committee Title

Committee Member

Keywords

Episodic Memory, Sequence Memory, Electrophysiology, DREADDs, Chemogenetics, Prefrontal Cortex, Hippocampus, Reuniens, Rats

Date of Defense

7-11-2022

Abstract

Our capacity to establish unique episodic memories rests largely on our ability to recall sequences of events. While different experiences might be comprised of the same objects (e.g., colleagues and a Zoom screen) and settings (e.g., the home or office), the unique temporal components of these experiences is what allows us to differentiate events in sequences. That is to say, memory critically includes information about “when” an event occurred, in addition to the “what” and “where”. Sequence memory provides a representation of the order of events as they occur within an experience and underlies our ability to “play-back” those experiences. However, the neurobiological underpinnings of the temporal organization of memory and behavior remains poorly understood. The focus of this dissertation is to understand the neurobiological role of the mPFC-HC circuit in sequence memory by using chemogenetics, electrophysiology, and optogenetics. In Chapter 1, I begin by reviewing the literature of the neurobiology of time in memory focusing on sequences of events. This chapter elaborates on candidate temporally-structured neural events that could underlie our ability to encode temporal content as well as some basic systems architecture for time in memory. In Chapter 2, I test the role of sex and estrous cycle in learning and overall performance on a new version of the cross-species validated sequence memory task using two odor sequences. Sex and estrous cycle were not major factors during training and testing stages of the sequence memory task. In Chapter 3, to further my investigations of the neurobiology of sequence memory I develop a novel 3D-printable stereotaxic device for rats called the RatHat. The RatHat provides more accuracy and reliability then traditional stereotaxic surgeries allowing for multisite implants critical to studying sequence memory. In Chapter 4, I explore the causal roles of mPFC projections to RE and PER using DREADDs (AAV-hM4Di) in sequence memory. I provide evidence showing that suppressing synaptic activity in the mPFC-to-RE or mPFC-to-PER pathway abolishes sequence memory demonstrating their critical roles, and that these pathways regulate ongoing retrieval strategies. In Chapter 5, I examine the local field potentials of sequence memory in mPFC, RE and HC. I found that RE neurons send monosynaptic projections to CA1 triggering mPFC-HC interactions in the beta band enabling network states conducive to successful memory-based decision making. Overall, this dissertation for the first time delivers a detailed understanding of the functional circuitry of mPFC-HC in the memory for sequences of events. It aims to aid in future investigations into mechanisms of temporal dysfunction in mental health disorders such as schizophrenia, ADHD, and/or Alzheimer's’s disease.

Identifier

FIDC010855

ORCID

https://orcid.org/0000-0002-3285-1622

Previously Published In

Jayachandran, M., Viena, T.D., Garcia, A., Veliz, A.V., Leyva, S., Roldan, V., Vertes, R.P. and Allen, T.A. (2022) Reuniens transiently synchronizes memory networks at beta frequencies. BioRxiv.

Jayachandran, M. & Allen, T.A. (2022). Candidate Neural Activity for the Encoding of Temporal Content in Memory. In Vertes, R. P., & Stackman, R. W. (Eds.) Electrophysiological recording techniques.

Jayachandran, M., Langius, P., Pazos Rego, F., Vertes R.P., Allen, T.A. (2022) Sex and Estrous Cycle in Memory for Sequences of Events in Rats. Behavioral Neuroscience.

Schlecht, M., Jayachandran, M., Rasch, G.E., Allen, T.A. (2022) Dual-projecting cells that link the thalamic and cortical pathways between the medial prefrontal cortex and hippocampus. Neurobiology of Learning and Memory, 188, 107586.

Jayachandran M.*, Allen L.M.*, Viena T.D., Meifung S., McNaughton, B.L., Allen T.A. (2020) RatHat: A self-targeting printable brain implant system. eNeuro, 7(2). *authors contributed equally.

Schultheiss, N.W., Schlecht, M., Jayachandran, M., Brooks, D.R., McGlothan, J.L., Guilarte, T.R. and Allen, T.A., (2020). 'Awake delta'and theta-rhythmic hippocampal network modes during intermittent locomotor behaviors in the rat. Behavioral Neuroscience, 134(6), 529-546.

Jayachandran M., Linley S.B., Schlecht M., Mahler S.V., Vertes R.P., Allen T.A. (2019) Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events. Cell reports, 28(3):640-54.

Recommended Citation

Jayachandran, Maanasa N., "The Role of Prefrontal-Hippocampal Circuit in the Memory for Sequences of Events" (2022). FIU Electronic Theses and Dissertations. 5224.
https://digitalcommons.fiu.edu/etd/5224