Presentation Title

Optogenetic Entrainment of the Septo-Hippocampal Circuit

Abstract

Theta oscillations in the hippocampus represent an important computational property of hippocampal function. Hippocampal theta oscillations are principally generated by the medial septum (MS), and previous findings have suggested that a subpopulation of cells within the MS entrain the firing patterns of downstream neurons in the hippocampus. Additionally, it is unclear whether exogenously imposed control of this peacemaking circuitry via optogenetic stimulation can supersede endogenous activity and whether the hippocampus can properly function given this artificial input. Using two lines of transgenic rats, we titrated the entrainment efficacy of increasingly finer cell populations by selectively stimulating either Gad-expressing (GABAergic) or parvalbumin-expressing (PV) neurons in the medial septum in awake rats with limited mobility. Stimulation of target neurons was performed in an oscillating manner thereby mimicking the endogenously produced cell activity intervals in the theta frequency band. While stimulating, intracranial EEG tetrodes simultaneously recorded the extracellular field potentials from both the medial septum and bilateral hippocampi. We found that MS stimulation of both GABAergic neurons, as well as a PV-positive subpopulation of GABAergic neurons, sufficiently entrained hippocampal theta oscillations at all theta frequencies (5-12Hz) in relatively immobile subjects. However, some recording electrodes detected a competition between endogenous (~7Hz) and exogenously generated frequencies. These findings suggest that it may be possible to impose a temporally precise control over the septo-hippocampal circuit using optogenetics in vivo, allowing further avenues of enquiry into the relationships between hippocampal theta, cognition, and behavior.

Primary Faculty Mentor Name

Jeremy M. Barry

Secondary Mentor NetID

jcoutinh

Secondary Mentor Name

Jaeda Coutinho-Budd

Status

Undergraduate

Student College

College of Arts and Sciences

Program/Major

Neuroscience

Primary Research Category

Biological Sciences

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Optogenetic Entrainment of the Septo-Hippocampal Circuit

Theta oscillations in the hippocampus represent an important computational property of hippocampal function. Hippocampal theta oscillations are principally generated by the medial septum (MS), and previous findings have suggested that a subpopulation of cells within the MS entrain the firing patterns of downstream neurons in the hippocampus. Additionally, it is unclear whether exogenously imposed control of this peacemaking circuitry via optogenetic stimulation can supersede endogenous activity and whether the hippocampus can properly function given this artificial input. Using two lines of transgenic rats, we titrated the entrainment efficacy of increasingly finer cell populations by selectively stimulating either Gad-expressing (GABAergic) or parvalbumin-expressing (PV) neurons in the medial septum in awake rats with limited mobility. Stimulation of target neurons was performed in an oscillating manner thereby mimicking the endogenously produced cell activity intervals in the theta frequency band. While stimulating, intracranial EEG tetrodes simultaneously recorded the extracellular field potentials from both the medial septum and bilateral hippocampi. We found that MS stimulation of both GABAergic neurons, as well as a PV-positive subpopulation of GABAergic neurons, sufficiently entrained hippocampal theta oscillations at all theta frequencies (5-12Hz) in relatively immobile subjects. However, some recording electrodes detected a competition between endogenous (~7Hz) and exogenously generated frequencies. These findings suggest that it may be possible to impose a temporally precise control over the septo-hippocampal circuit using optogenetics in vivo, allowing further avenues of enquiry into the relationships between hippocampal theta, cognition, and behavior.