The Maturational Development of Entorhinal-hippocampal Oscillations and the Effects of
recurrent Early-life Seizure on CA1 Signal Coordination
Abstract number :
2.058
Submission category :
3. Neurophysiology / 3F. Animal Studies
Year :
2022
Submission ID :
2204760
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:26 AM
Authors :
Conor Dickson, BS – UVM; Jeremy Barry, PhD – Assistant Professor, Neuroloigcal Sciences, UVM; Natalie Cashen, BS – Tech, Neuroloigcal Sciences, UVM; Gregory Holmes, MD – Neuroloigcal Sciences – UVM
Rationale: The hippocampus and entorhinal cortex are components of a network whose effective interaction is dependent on the temporal coordination of current oscillations along the CA1 and dentate gyrus (DG) somatodendritic axes. The orchestrated development of intra-hippocampal and cortico-hippocampal synaptic connectivity, dendritic maturation and their governance by local interneurons has become increasingly better understood. However, little is known about how these developmental processes are disrupted by recurrent early-life seizures (ELS). Moreover, although cognitive deficits have been connected to altered cortico-hippocampal signal coordination in adult ELS animals, it remains unclear if these changes develop as a function of maturation or are set in place shortly after seizure onset. We therefore aimed to characterize CA1 and DG theta and gamma oscillation properties along each somatodendritic axis, as both a function of ELS induction and developmental maturation.
Methods: P15 to P24 Sprague-Dawley rat pups underwent ELS induction consisting of 5 flurothyl inhalation seizures a day over a 10-day period. Control animals (CTL) were separated from dames for an equal time period to control for maternal separation effects. We conducted high-density laminar silicon probe recordings (64 channel, H3 Cambridge Neurotech) from ELS and CTL animals at P23 and >P90 (juveniles: ELS=6, CTL=5; adults: ELS=3). To study baseline physiology of the hippocampal circuit without the influence of behavior, recordings were conducted under urethane anesthesia. Wideband EEG recordings measured activity from CA1, DG and hilus during tail-pinch stimulation driven slow-theta oscillations (2-5 Hz) in the entorhinal-hippocampal circuit. Signal amplitude and frequency properties, cross-frequency coupling (CFC), phase coherence, and current source density (CSD) were then analyzed as a function of depth for each bandwidth of interest.
Results: Remarkably, tail pinch stimulation induction of slow theta in CA1 str. lacunosum moleculare and the DG outer molecular layers were consistent across groups, regardless of age or experimental condition. However, preliminary results also indicated that in both ELS juveniles and ELS adults, theta and gamma oscillation power, CSD and CFC levels were significantly increased in str. radiatum, whereas there was a sharp decrease in these theta and gamma properties in the CA1 pyramidal cell layer.
Conclusions: The results suggest that: (1) L3 medial entorhinal and L2 lateral entorhinal synaptic projections to hippocampus are functionally intact at P23 and potentially unaffected by ELS; (2) The altered properties of str. radiatum theta and gamma suggest changes in intrahippocampal connectivity via the Schaffer collaterals or attenuated local inhibitory regulation via bistratified interneurons. This effect could interfere with propagation and signal coordination along the CA1 somatodendritic axis to the pyramidal cell layer; and (3) Altered str. radiatum signals in ELS adults and juveniles indicates this change likely began after ELS induction and persist into adulthood.
Funding: NIH Grants NS108765 and NS108296 to JMB and GLH
Neurophysiology