bioRxiv Science⌕ Search

bioRxiv · 10.1101/513911

Recruitment and disruption of value encoding during alcohol seeking

Abstract

A critical area of inquiry in the neurobiology of alcohol abuse is the neural mechanisms by which cues gain the ability to elicit alcohol use. We previously showed that cue-evoked activity in rat ventral pallidum (VP) robustly encodes the value of cues trained under both Pavlovian and instrumental contingencies, despite a stronger relationship between cue-evoked responses and behavioral latency after instrumental training. Here, we assessed VP neural representations of cue value in rats trained with a Pavlovian conditioned stimulus (CS+) that predicted alcohol delivery, and in rats trained with an instrumental discriminative stimulus (DS) that predicted alcohol availability if the rat entered the reward port during the cue. We also examined the impact of alcohol exposure itself on the integrity of this type of signaling in rats trained with sucrose. Decoding of cue value based on VP firing was blunted for an alcohol CS+ versus an alcohol DS, as well as in comparison to a sucrose DS or CS+. Further, homecage alcohol exposure had opposing effects on VP encoding of cue value for a sucrose DS versus a sucrose CS+, enhancing decoding accuracy for the DS and reducing decoding accuracy for the CS+. These findings suggest that problem alcohol seeking may result from biased engagement of specific reward-related processes via changes in VP signaling.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ottenheimer, D., Wang, K., Haimbaugh, A., Janak, P. H., Richard, J. M.. 2019-01-07. Recruitment and disruption of value encoding during alcohol seeking. https://doi.org/10.1101/513911

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

KEEP EXPLORING

Related preprints

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↗

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↗

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↗