Biology subjects

Power, J. M.

Publications and source records attributed to Power, J. M..

7 recordsLinked to original sources

bioRxiv2025

Instrumental Punishment Learning Enhances the Intrinsic Excitability of Basolateral Amygdala Neurons

The basolateral amygdala (BLA) is a structure that is critical for forming Pavlovian and instrumental emotional associations. Previous studies have established that Pavlovian fear conditioning increases the intrinsic excitability of BLA projection neurons. Learning-associated increases in excitability are hypothesised to facilitate the induction of synaptic plasticity and integration of neurons into functional learning circuits. Here, we examined whether instrumental learning produces similar changes in intrinsic excitability. Male and Female Long Evans rats were trained to lever press for a food reward and subsequently split into 3 behavioural groups; punished, yoked, and reward. Punished rats received response-contingent footshocks, yoked rats received response-independent footshocks, and reward rats received no shock. Intrinsic excitability was measured as the number of action potentials (APs) evoked by a series of depolarising current injections during whole-cell patch clamp recordings. Reward learning increased the intrinsic excitability of BLA projection neurons compared to naive controls. Punishment training maintained excitability and excitability was correlated with performance on the punishment task. Response-independent footshocks arrested reward-associated increases in excitability, reverting the BLA neurons to a naive state. Group differences were observed in AP half-width and the current underlying the post-burst AHP. Together, these findings show that instrumental reward learning enhances the intrinsic excitability of BLA projection neurons, potentially supporting action-outcome encoding by promoting synaptic plasticity and circuit integration. The results also suggest that different forms of learning engage distinct biophysical adaptations. A mechanistic understanding of the neurobiology underlying instrumental association learning may help inform the development of treatments for psychiatric disorders characterized by deficits in this process, such as major depressive disorder and conduct disorder.

neuroscience↗

bioRxiv2021

Sex-Dependent Effects of Chronic Microdrive Implantation on Acquisition of Trace Eyeblink Conditioning

Neuroscience techniques, including in vivo recording, have allowed for a great expansion in knowledge; however, this technology may also affect the very phenomena researchers set out to investigate. Including both female and male mice in our associative learning experiments shed light on sex differences on the impact of chronic implantation of tetrodes on learning. While previous research showed intact female mice acquired trace eyeblink conditioning faster than male and ovariectomized females, implantation of chronic microdrive arrays showed sexually dimorphic effects on learning. Microdrive implanted male mice acquired the associative learning paradigm faster than both intact and ovariectomized females. These effects were not due to the weight of the drive alone, as there were no significant sex-differences in learning of animals that received "dummy drive" implants without tetrodes lowered into the brain. Tandem mass tag mass spectrometry and western blot analysis suggest that significant alterations in the MAPK pathway, acute inflammation, and brain derived neurotrophic factor may underlie these observed sex- and surgery-dependent effects on learning.

neuroscience↗

bioRxiv2020

Phasic inhibition of dopamine neurons is an instrumental punisher

It is well established that the activity of VTA dopamine neurons is sufficient to serve as a Pavlovian reinforcer but whether this activity can also serve as instrumental reinforcer is less well understood. Here we studied the effects of optogenetic inhibition of VTA dopamine neurons in instrumental conditioning preparations. We show that optogenetic inhibition of VTA dopamine neurons causes a response-specific, contingency-sensitive suppression of instrumental responding. This suppression was due to instrumental response, not Pavlovian stimulus, learning and could not be attributed to deepened instrumental extinction learning. These effects of optogenetic inhibition of VTA dopamine neurons on instrumental responding are formally similar to the effects of aversive events in instrumental preparations and show that optogenetic inhibition of VTA dopamine neurons is sufficient to serve as an instrumental punisher.

neuroscience↗

bioRxiv2020

The mesolimbic dopamine signatures of relapse to alcohol-seeking

The mesolimbic dopamine system comprises distinct compartments supporting different functions in learning and motivation. Less well understood is how complex addiction-related behaviors emerge from activity patterns across these compartments. Here we show how different forms of relapse to alcohol-seeking are assembled from activity across the ventral tegmental area and the nucleus accumbens. Using gCaMP and dLight fibre photometry, we show that self-administration and two forms of relapse (renewal/context-induced reinstatement and reacquisition) are associated with recruitment across the mesolimbic dopamine system. Using a variety of interventions, we show that this activity is causal to both forms of relapse. Finally, we use dissimilarity matrices to identify mesolimbic dopamine signatures of self-administration, extinction, and relapse. We show that signatures of relapse can be identified from heterogeneous activity profiles across the mesolimbic dopamine system and that these signatures differ for different forms of relapse.

neuroscience↗

bioRxiv2019

Complementary roles for ventral pallidum cell types and their projections in relapse

Ventral pallidum (VP) is a key node in the neural circuits controlling relapse to drug seeking but how this role relates to different VP cell types and their projections is poorly understood. Using male rats, we show how different forms of relapse to alcohol-seeking are assembled from VP cell types and their projections to lateral hypothalamus (LH) and ventral tegmental area (VTA). First, we used RNAScope in situ hybridization to characterize activity of different VP cell types during relapse to alcohol-seeking provoked by renewal (context-induced reinstatement). We found that VP Gad1 and parvalbumin (PV), but not vGlut2, neurons show relapse-associated changes in c-Fos expression. Next, we used retrograde tracing, chemogenetic, optogenetic, and electrophysiological approaches to study the roles of VPGad1 and VPPV neurons in relapse. We show that VPGad1 neurons contribute to contextual control over relapse (renewal), but not to relapse during reacquisition, via projections to LH where they converge with ventral striatal inputs onto LHGad1 neurons. This convergence of striatopallidal inputs at the level of individual LHGad1 neurons may be critical to balancing propensity for relapse versus abstinence. In contrast, VPPV neurons contribute to relapse during both renewal and reacquisition via projections to VTA but not LH. These findings show complementary roles for different VP cell types and their projections in relapse. VPGad1 neurons control relapse during renewal via projections to LH whereas VPPV neurons control relapse during both renewal and reacquisition via projections to VTA. Targeting these different pathways may provide tailored interventions for different forms of relapse.

neuroscience↗

bioRxiv2018

Conditional upregulation of KCC2 selectively enhances neuronal inhibition during seizures

Abstract/SummaryEfficacious neuronal inhibition is sustained by the neuronal K+Cl- co-transporter KCC2, and loss of KCC2 function through injury or mutation is associated with altered GABAergic signalling and neuronal seizures. Here we report a transgenic mouse with conditional KCC2 overexpression that results in increased membrane transport function. Increased KCC2 has little impact on behavioural and in vitro assays of neuronal excitability and GABAA receptor responses under resting conditions. In contrast, increased KCC2 imparts resistance to seizure-like neuronal activity in hippocampal slices and prevents the progression of mice into behavioural status epilepticus following multiple kainic acid doses. Our results demonstrate a transgenic mouse to facilitate investigations into the role of KCC2 in brain function, and provide a proof of principle that targeting KCC2 may be an effective way to selectively enhance neuronal inhibition to mitigate against diseases that involve an imbalance between excitation and inhibition.

neuroscience↗

bioRxiv2017

Basolateral amygdala glutamatergic neurons maintain aversive emotional salience

Basolateral amygdala (BLA) glutamatergic neurons serve a well-accepted role in fear conditioning and fear extinction. However, the specific learning processes related to their activity at different times during learning remain poorly understood. We addressed this using behavioral tasks isolating distinct aspects of fear learning in rats. We show that brief optogenetic inhibition of BLA glutamatergic neurons around moments of aversive reinforcement or non-reinforcement causes reductions in the salience of conditioned stimuli, rendering these stimuli less able to be learned about and less able to control fear or safety behaviours. This salience reduction was stimulus-specific, long-lasting, and specific to aversive emotional states - precisely the goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition. They show that a primary function of BLA glutamatergic neurons is to maintain the salience of conditioned stimuli. This is a necessary precursor for these stimuli to gain and maintain control over fear and safety behavior.\n\nSignificance statementThe amygdala is essential for learning to fear and learning to reduce fear. However, the specific roles served by activity of different amygdala neurons at different times during learning is poorly understood. We used behavioral tasks isolating distinct aspects of learning in rats to show that brief optogenetic inhibition of BLA glutamatergic neurons around moments of reinforcement or non-reinforcement disrupts maintenance of conditioned stimulus (CS) salience. This causes a stimulus-specific, long-lasting, and aversive emotion specific deficit in the ability of the CS to be learned about or control fear responses. These consequences are the precisely goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition.

neuroscience↗