Chronic Methamphetamine Alters Neural Oscillations and Population Spikes Associated with Synaptic Plasticity, thus Long- Term Potentiation in the Guinea Pig Hippocampus, in vivo

Author

Jaclyn Locigno, Philadelphia College of Osteopathic Medicine

Date of Award

7-2021

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Adwoa Dansoa Aduonum PhD

Second Advisor

Sanika Chirwa PhD

Third Advisor

Richard E. White, Ph.D., FAHA

Fourth Advisor

Shu Zhu, MD, Ph.D.

Fifth Advisor

Lori Redmond, Ph.D.

Abstract

Chronic methamphetamine (METH) users perform poorly compared to controls on tasks of verbal and nonverbal memory, recognition, attention, and decision-making. The neural mechanisms that underlie these cognitive deficits are unclear. This was the focus of the study presented here. We treated male guinea pigs with 10 mg/kg/day METH (N=12) or phosphate buffered saline (PBS, N= 8) for 7 days. Drugs were administered as a continuous infusion using ALZET mini-pumps. After 7 days of treatment a subset of guinea pigs from each group (METH = 6 and PBS = 4) were anesthetized with urethane (1500 mg/kg) and local field potentials and evoked population spikes across the CA₃/CA₁ synapses were obtained from the hippocampus in vivo. Similar recordings were conducted in the remaining subset of guinea pigs (i.e., METH = 6 and PBS = 4) after 7 days of drug washout. We found that METH-treated guinea pigs exhibited increased spontaneous CA₁ cell discharges and had diminished slow wave oscillations. By contrast, PBS controls exhibited fewer spontaneous discharges and had prominent slow wave oscillations whose peaks were inundated with robust ‘ripples’, a hallmark of transfer of information from the hippocampus to neocortical structures. We also found that long-term potentiation (LTP, a cellular correlate of learning and memory) was attenuated in the METH-treated guinea pigs when compared to PBS controls. The effects of METH on CA₁ cell discharges, oscillations, and LTP were amplified after the 7-day washout. The amplification of the effects during the washout period may be caused by the depletion of METH’s neuroprotective factors. Taken together, our results raise the possibility that METH-induced changes in CA₁ network properties may partly underlie the reported memory impairments associated with the drug.

Recommended Citation

Locigno, Jaclyn, "Chronic Methamphetamine Alters Neural Oscillations and Population Spikes Associated with Synaptic Plasticity, thus Long- Term Potentiation in the Guinea Pig Hippocampus, in vivo" (2021). PCOM Biomedical Studies Student Scholarship. 205.
https://digitalcommons.pcom.edu/biomed/205