Biology subjects

Carmichael, J. E.

Publications and source records attributed to Carmichael, J. E..

10 recordsLinked to original sources

bioRxiv2026

Medial septum glutamatergic neurons support speed coding and grid cell spatial stability in the medial entorhinal cortex

Successful navigation requires the integration of self-motion signals with spatial representations, yet the circuits that provide velocity information necessary for stable grid cell firing remain incompletely understood. Here, we identify medial septal (MS) glutamatergic neurons as a critical component of this pathway. Using cell-type-specific optogenetic silencing combined with in vivo electrophysiology in freely moving mice, we show that MS glutamatergic neurons support the fidelity of firing rate-based speed coding in the medial entorhinal cortex (MEC). Silencing this population reduced grid cell spatial periodicity and stability and produced distortions of grid firing fields. Silencing also reduced theta phase-locking strength in strongly theta-modulated MEC neurons. Model simulations of a hybrid oscillatory interference-continuous attractor network with reductions in speed-signal fidelity disrupted grid periodicity and reproduced features of the spatial distortions observed in vivo. Together, these findings identify a septo-entorhinal circuit that coordinates self-motion information with the spatial and temporal organization of MEC activity to maintain a stable neural representation of space.

neuroscience↗

bioRxiv2024

Structured and unstructured reactivations during REM sleep are modulated by novel experiences

Mammalian sleep alternates between rapid eye movement (REM) and non-REM (NREM) phases, each with distinct patterns of neural activity. The replay of waking experience during NREM sleep is a well-established substrate for memory consolidation, but whether comparable reactivation occurs during REM sleep has remained unclear, owing to the sparse firing that characterizes this state and the lack of robust methods for detecting replay within it. Here we combined calcium imaging with electrophysiology to monitor large populations of hippocampal CA1 neurons in mice and applied complementary analytical approaches to test for neural reactivation during REM sleep. We found that structured waking activity is re-expressed during REM sleep across a range of temporal organizations, from the reactivation of co-active cell assemblies to temporally ordered sequential replay. This reactivation was selectively shaped by the behavioral context of prior experience. Novel experience enhanced sequential replay and refined assembly composition, selectively reducing the participation of weakly contributing neurons; anxiogenic experience, by contrast, increased the frequency of assembly reactivation and reinforced the recruitment of strongly contributing neurons. REM sleep thus emerges as an active stage of memory processing that reorganizes recent experience according to its behavioral significance, engaging distinct operations for novel and for emotionally salient events.

neuroscience↗

bioRxiv2024

Habit learning shapes activity dynamics in the central nucleus of the amygdala

As animals perform instrumental tasks, they may develop a habit response with extended experience. Habits are automatic, inflexible, outcome value insensitive behaviors that are regulated by a network of brain regions including the central nucleus of the amygdala (CeA). Prior work has demonstrated that the CeA governs motivational pursuit and is necessary for habit formation. However, the behavioral features that CeA neurons encode in habit formation remain relatively unknown. To address this, we first used male and female Long-Evans rats to quantify CeA cFos expression after performance of a maze task. There, we found that animals with extended training show elevated cFos expression. Then, we implanted animals with drivable silicon probes to record in-vivo single unit electrophysiological activity from the CeA as animals developed habit responding on the maze. We observed significant activity during outcome consumption late in training while also observing elevated unit activity when animals consumed outcomes of larger magnitudes. Outcome related activity did not persist during probe tests following outcome devaluation, despite animals continuing to perform the task. Together, these data add to growing evidence that suggests that the CeA is involved in motivational processes that contribute to the development of habit formation.

neuroscience↗

bioRxiv2024

Optogenetic mapping of rhythmic phase-dependentexcitability in the mouse striatum

The striatum is thought to switch flexibly between multiple converging inputs to support adaptive behavior. The "communication through coherence" (CTC) hypothesis is a potential mechanism to implement such a flexible switching. For CTC to work in the striatum, striatal excitability must show rhythmic fluctuations, such as those related to the phase of the striatal local field potential (LFP). To test this fundamental requirement, we delivered a constant input stimulus to ChR2-expressing striatal fast-spiking PV+ interneurons (FSIs) in head-fixed awake mice (PV-Cre:Ai-32, n = 18, 9 female), and determined whether the response to this stimulus varied with LFP phase. We found that approximately one-third (41.2%) of FSIs exhibited significant phase-dependent excitability in at least one LFP frequency band. Phase-dependent excitability was most prominent in the delta (2-5 Hz) frequency band, both in terms of prevalence (23.5% of FSIs sampled) and magnitude (phase modulation strength: 22% of average response). The most excitable phase tended to align with endogenous phase-locking, again most clearly in the delta band. These results bolster the functional relevance of the striatal field potential and spike-field relationships, and provide proof-of-principle support for the possibility of CTC in the striatum. Significance StatementThe striatum is thought to switch dynamically between multiple converging inputs. A leading idea for how this is accomplished is through communication through coherence (CTC). A fundamental, but previously untested, requirement for CTC to work is that striatum must show changes in excitability that depend on local field potential phase. We find that about one-third of striatal neurons show phase-dependent excitability, providing proof of principle for CTC-like switching in striatum.

neuroscience↗

bioRxiv2022

Spatial memory consolidation during REM sleep requires stabilization of newly formed place cells.

The involvement of rapid-eye-movement sleep (REMs) in spatial memory formation was recently demonstrated, although how neural activity during REMs influences newly-formed place field stability remains unclear. Here, we combined large-scale single-unit recordings of mouse hippocampal CA1 with an established optogenetic approach enabling REMs-selective inhibition of medial septum GABAergic neurons (MSGABA), resulting in spatial memory deficits when applied post-learning. Although individual neural activity was unaffected by REMs-selective MSGABA inhibition during a post-learning rest session, both the synchrony of population-level activity bursts observed during REMs occurring in the rest session and place field stability measured during subsequent memory recall testing were reduced vs controls. However, the latter effect was limited to place cells participating in population activity during REMs, as stability of non-participant place cells was relatively weak and indifferent between groups. This suggests that synchronous CA1 population activity during REMs stabilizes spatial representations in a plastic subpopulation of participating CA1 neurons.

neuroscience↗

bioRxiv2019

Piriform cortex provides a dominant gamma LFP oscillation in the anterior limbic system

Oscillations in the local field potential (LFP) are widespread throughout the rodent limbic system, including in structures such as the orbitofrontal cortex and nucleus accumbens. Synchrony between LFPs across these structures, as seen during specific behavioral events, is often interpreted as evidence of a functional interaction. However, the source of these oscillations is often tacitly assumed to be local, leading to a potential misattribution of function. Using in vivo simultaneous multisite recordings in freely moving male rats (n = 7) we demonstrate that gamma-band LFP oscillations (45-90 Hz) in multiple anterior limbic structures are highly synchronous not only with each other, but also with those in piriform cortex. Phase reversals across the piriform cortex cell layer and susceptibility to nasal occlusion indicate that piriform cortex is the source of these common gamma oscillations. Thus, gamma-band LFP oscillations seen in brain regions adjacent to the piriform cortex are likely not generated locally, but are instead volume conducted from the piriform cortex. This emerging view of gamma oscillations in anterior limbic circuits highlights the importance of the common piriform cortex input as a major influence and introduces caveats in the interpretation of locally recorded LFPs.

neuroscience↗

bioRxiv2019

A comprehensive characterization of rhythmic spiking activity in the rat ventral striatum

The ventral striatum (vStr) is anatomically interconnected with brain structures that exhibit prominent rhythmic activity, suggesting that oscillations in ventral striatal activity are potentially informative about systems-level interactions between these structures. However, rhythmic activity in ventral striatal neurons during behavior has only been characterized piecemeal, with individual studies focusing on a single cell type or frequency band. We performed a comprehensive analysis of (1) rhythmic activity in vStr neurons without reference to the local field potential, and (2) average as well as time-resolved spike-field relationships. Spike train rhythmicity tended to be limited to low frequencies such as delta and theta, whereas spike-field relationships were seen across a broad spectrum of frequencies, with about 90% of neurons showing spike-field locking to at least one rhythm. Using a novel time-resolved generalized linear model approach, we further show that the contribution of local field potential (LFP) phase to spike timing is dynamic over time, and enhanced by the inclusion of the LFP from the hippocampus - a new measure of inter-area coupling. These results provide a foundation for a more accurate interpretation of the ventral striatal LFP, suggest the possibility of an oscillatory taxonomy of ventral striatal neurons, and provide a starting point for understanding how rhythmic activity links cell-, circuit-, and systems-level phenomena in the ventral striatum.\n\nSignificance StatementOscillations in neural activity are ubiquitous in the brain, readily accessible in the clinic and the lab, and shared by humans and animals to facilitate translational work. The ventral striatum (vStr) is a promising target structure for such a rhythmic activity perspective, not in the least because its local field potential (LFP) shows prominent task-related oscillations across a range of frequencies. However, recent work has shown that major components of the vStr LFP are in fact generated elsewhere in the brain, raising the question of how the LFP relates to local spiking activity. Unlike previous studies that focused on a specific cell type or frequency band of interest, we characterize rhythmic activity across a full range range of frequencies and cell types, and include novel analyses appropriate for a non-local LFP. Our results provide a foundation for more accurate interpretation of the vStr LFP and a starting point for an oscillatory taxonomy of vStr neurons.

neuroscience↗

bioRxiv2018

The dorsolateral striatum regulates habits by way of performance vigor when actions are initiated

Despite clear evidence linking basal ganglia control to habits, it remains unclear through what mechanisms this control occurs. Here, we demonstrate that a key function of the dorsolateral striatum (DLS) is to regulate the vigor of a learned behavior at the moment of initiation in a habit-promoting manner. Shifts in vigor by phasic DLS perturbations coincide closely with how outcome-insensitive (i.e., habitual) the behaviors are in both response-based and cue-based task situations. Surprisingly, the control over habit strength by way of changes in vigor occurs without consistent changes in accuracy, suggesting that mechanisms controlling habit and vigor are dissociable from performance governed task rules. Finally, we show that increased DLS activity improves vigor preferentially when learned outcome values are stable, while reduced DLS activity dampens vigor preferentially when outcome values change. These data indicate that improving action vigor could be a principle route by which the basal ganglia facilitate habits.

animal behavior and cognition↗

bioRxiv2018

Persistent coding of outcome-predictive cue features in the rat nucleus accumbens

The nucleus accumbens (NAc) is important for learning from feedback, and for biasing and invigorating behavior in response to cues that predict motivationally relevant outcomes. NAc encodes outcome-related cue features such as the magnitude and identity of reward. However, little is known about how features of cues themselves are encoded. We designed a decision making task where rats learned multiple sets of outcome-predictive cues, and recorded single-unit activity in the NAc during performance. We found that coding of cue identity and location occurred alongside coding of expected outcome. Furthermore, this coding persisted both during a delay period, after the rat made a decision and was waiting for an outcome, and after the outcome was revealed. Encoding of cue features in the NAc may enable contextual modulation of ongoing behavior, and provide an eligibility trace of outcome-predictive stimuli for updating stimulus-outcome associations to inform future behavior.

neuroscience↗

bioRxiv2017

Gamma Oscillations In The Rat Ventral Striatum Originate In The Piriform Cortex

Local field potentials (LFP) recorded from the human and rodent ventral striatum (vStr) exhibit prominent, behaviorally relevant gamma-band oscillations. These oscillations are related to local spiking activity and transiently synchronize with anatomically related areas, suggesting a possible role in organizing vStr activity. However, the origin of vStr gamma is unknown. We recorded vStr gamma oscillations across a 1.4mm2 grid spanned by 64 recording electrodes as rats rested and foraged for rewards, revealing a highly consistent power gradient originating in the adjacent piriform cortex. Phase differences across the vStr were consistently small (<10{degrees}) and current source density analysis further confirmed the absence of local sink-source pairs in the vStr. Reversible occlusions of the ipsilateral (but not contralateral) nostril, known to abolish gamma oscillations in the piriform cortex, strongly reduced vStr gamma power and the occurrence of transient gamma-band events. These results imply that local circuitry is not a major contributor to gamma oscillations in the vStr LFP, and that piriform cortex is an important driver of gamma-band oscillations in the vStr and associated limbic areas.\n\nSignificance StatementThe ventral striatum is an area of anatomical convergence in circuits underlying motivated behavior, but it remains unclear how its inputs from different sources interact. One of the major proposals of how neural circuits may dynamically switch between convergent inputs is through temporal organization reflected in local field potential (LFP) oscillations. Our results show that in the rat, the mechanisms controlling vStr gamma oscillations are primarily located in the in the adjacent piriform cortex, rather than vStr itself. This provides a novel interpretation of previous rodent work on gamma oscillations in the vStr and related circuits, and an important consideration for future work seeking to use oscillations in these areas as biomarkers in rodent models of human behavioral and neurological disorders.

neuroscience↗