bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/558189

Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons

McGinnis, M. M.·Parrish, B. C.·Chappell, A. M.·McCool, B. A.
View original source ↗Export metadata ↓

Abstract

The medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) have strong reciprocal connectivity. Projections from the BLA to the mPFC can bidirectionally modulate anxiety-related behaviors but it is unclear if the same is true for mPFC to BLA projections. Our laboratory is specifically interested in withdrawal-related anxiety-like behavior and the underlying synaptic plasticity. Here, we use optogenetics and chemogenetics to characterize the neurophysiological and behavioral alterations produced by chronic ethanol exposure and withdrawal on dorsal mPFC/prelimbic (dmPFC/PL) and ventral mPFC (vmPFC/IL) terminals in the BLA. We exposed adult male Sprague-Dawley rats to chronic intermittent ethanol (CIE) using vapor chambers, measured anxiety-like behavior on the elevated zero maze (EZM), and used electrophysiology to record glutamatergic and GABAergic responses in BLA principal neurons. We found that 24-hour withdrawal following a 7-day CIE exposure significantly increased the glutamate release probability from PL/dmPFC terminals, but significantly decreases the glutamate release probability from IL/vmPFC terminals. Chemogenetic inhibition of PL/dmPFC terminals in the BLA attenuated the increased withdrawal-dependent, anxiety-like behavior. These data demonstrate that chronic ethanol exposure and withdrawal strengthens the PL/dmPFC - BLA pathway but weakens the IL/vmPFC - BLA pathway. Moreover, we provide novel evidence that the PL/dmPFC - BLA pathway can modulate anxiety-like behavior. These findings suggest that mPFC-BLA circuits known to regulate the acquisition of aversive behaviors are up-regulated by chronic ethanol while those involved with the extinction of these behaviors are down-regulated. Significance StatementAccumulating evidence suggests that the medial prefrontal cortex and its projections to the basolateral amygdala bidirectionally modulate fear-related behaviors. Since the neuronal circuits for fear and anxiety are thought to overlap, we sought to examine the role of prelimbic and infralimbic subdivisions of the medial prefrontal cortex and their inputs to the basolateral amygdala in regulating anxiety. Specifically, we focused on alcohol withdrawal-induced anxiety-like behavior, which is a commonly reported cause of relapse in human alcoholics. In our study, we used optogenetics and chemogenetics to demonstrate, for the first time, that withdrawal from chronic ethanol exposure strengthens prelimbic synapses, but weakens infralimbic synapses in the basolateral amygdala and that inhibiting glutamate release from prelimbic terminal in the basolateral amygdala reduces anxiety-like behavior.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

McGinnis, M. M., Parrish, B. C., Chappell, A. M., McCool, B. A.. 2019-02-22. Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons. https://doi.org/10.1101/558189

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Next generation Human Neocortical Neurosolver model with biophysically realistic somatic, dendritic and synaptic dynamics

The Human Neocortical Neurosolver (HNN) is an open-source biophysical modeling tool for multiscale interpretation of human electroencephalography (EEG) and magnetoencephalography (MEG) signals. HNN's foundation is a pre-tuned canonical neocortical circuit model consisting of excitatory pyramidal neurons and inhibitory interneurons in supra- (L2/3) and infragranular (L5) layers. This model was originally developed based on studies in rodent and non-human primate cortices when dynamics of human neurons were poorly characterized. Yet recent advances in recordings from human tissue now provide unprecedented detail to update the model. Here, we present a significantly updated model for use in the HNN software, with electrophysiological properties and synaptic connections tuned to human tissue. Beyond reproducing biologically realistic somatic dynamics, the pyramidal cells simulate dendritic calcium (Ca2+) spikes in the L5 extratelencephalic-projecting (ET) neurons, and shorter dendritic spikes in the L2/3 pyramidal neurons. We demonstrate how the updated circuitry and new features in the HNN software can be used to disentangle somatic, synaptic, and dendritic contributions to human E-/MEG signatures. The model is distributed with workflows to simulate event-related responses and oscillations, and tutorials demonstrating how membrane potentials, Ca2+ dynamics, and synaptic currents can be recorded and visualized. These enhancements allow extensive model validations based on in vitro and in vivo electrophysiology, voltage and Ca2+ imaging, and provide users with novel insights on the mechanisms underlying E-/MEG signals.

neuroscience↗
bioRxiv2026

A biological light sheet links cellular voltage to mesoscopic brain dynamics

Membrane voltage is the fundamental currency of neural computation, yet cellular-resolution voltage imaging of large neuronal populations in vivo remains limited by trade-offs among imaging speed, field of view, and optical sectioning. We overcome this challenge by encoding a biological light sheet in the brain: Selective Plane Expression (SPress) restricts fluorescent indicator expression to a user-defined, 20-m-thick plane, suppressing background at its source. Following one-time two-photon photoactivation, SPress enables standard widefield microscopes to capture high-contrast kilohertz voltage dynamics from hundreds of densely labeled neurons across millimeter-scale cortical sheets and columns in vivo. These recordings reveal mesoscopic subthreshold waves that flexibly reorganize population-wide spike timing, together with cellularscale wavefront microstructure that preserves stereotyped local recruitment biases. By shifting optical sectioning from instrumentation to gene expression, SPress makes kilohertz cellular resolution voltage imaging accessible across mesoscopic scales.

neuroscience↗
bioRxiv2026

Persistent hippocampal traces of lifelong spatial memory

Memory presents a biological paradox: the brain changes continuously, yet a brief experience can influence behavior for a lifetime. How such memories are stored in brain circuits remains unclear. Here we show that two days in a binary-tree maze leave mice with spatial memories that survive repeated 90-day absences over as much as a year. Across return visits, mice explored the maze more efficiently than when naive and resumed direct runs to a reward location sooner, both by a factor of 3. Chronic calcium imaging of the same hippocampal CA1 neurons showed that although most neurons had changed their preferred locations, the population activity at a given maze location still resembled the pattern from 90 days earlier. Furthermore, even when a neuron's place fields changed location, they tended to remain at the same branching level of the binary tree, reflecting the local geometry of the maze. In return sessions where the neural tuning for branching level was preserved more accurately, the mouse explored the environment more efficiently. Population patterns were best preserved near the reward location, and more reliable neural activity there accompanied earlier direct runs to the reward. With repeated experience, spatial representations changed less, both within a visit and across the long absences. A brief experience thus left selective hippocampal traces that survived months of absence despite drift, grew more durable with each return, and were correlated with memory in navigation behavior.

neuroscience↗