Biology subjects

Leung, B. K.

Publications and source records attributed to Leung, B. K..

5 recordsLinked to original sources

bioRxiv2026

Distinct amygdala-striatal and amygdala-cortical circuits encode and retrieve predictive learning to guide choice and decision-making

It has long been known that Pavlovian cues can influence choice between instrumental actions, although how this is achieved at a neural level is not fully understood. Here we examined the neural processes engaged during the encoding and retrieval of the Pavlovian stimulus-outcome (S-O) associations prior to and during their influence on choice. Using a Pavlovian-instrumental transfer paradigm (PIT), we found, as previously reported, that a circuit connecting the basolateral amygdala (BLA) and nucleus accumbens shell (BLA[->]NAc-S) is necessary to encode specific S-O associations within the NAc-S. However, this circuit was not required for the retrieval of those associations: optogenetic inhibition of this circuit had no effect on the ability of specific S-O associations to influence choice between instrumental actions. The BLA also projects to the infralimbic cortex (IL) although, using circuit mapping, we found that this projection was largely independent of the projection to the NAc-S. Nevertheless, using a circuit-specific disconnection approach, we found that the BLA[->]IL circuit is necessary for both the encoding and retrieval of specific S-O associations to influence choice. Furthermore, expanding on this disconnection approach, optogenetic inhibition of the BLA[->]IL circuit in one hemisphere and the IL[->]NAc-S contralaterally provided evidence that the broader BLA[->]IL[->]NAc-S circuit is necessary to retrieve specific S-O associations to influence choice during PIT. These data reveal, therefore, evidence of an amygdala-cortico-striatal circuit necessary for the retrieval of predictive learning to influence choice that differs from the circuit involved in encoding those predictive associations.

animal behavior and cognition↗

bioRxiv2026

Intratelencephalic neurons in the medial prefrontal cortex mediate the acquisition of goal-directed actions.

The medial prefrontal cortex (mPFC) and its connections with the posterior dorsomedial striatum are implicated in goal-directed learning, but the specific mPFC cell types involved have not been clearly established. The current study investigated mPFC intratelencephalic (IT) and pyramidal tract (PT) neuron involvement in goal-directed learning. In Cre-driver mouse lines, we mapped bilaterally projecting IT neurons and unilaterally projecting PT neurons from mPFC to dorsal striatum and showed that chemogenetic inhibition of IT, but not PT neurons, attenuated goal-directed learning. We then demonstrated training induced elevations in pERK signaling in IT neurons, which were transient in superficial mPFC layers, and more persistent in deeper layers. This was associated with plasticity in deep layer IT neurons, reflected in a shift towards excitatory over inhibitory synaptic inputs. Together, these data suggest that goal-directed learning influences synaptic input and downstream plasticity markers in mPFC IT neurons, and this functionally contributes to goal-directed learning.

neuroscience↗

bioRxiv2025

The influence of nucleus accumbens shell D1 and D2 neurons on outcome-specific Pavlovian instrumental transfer

The nucleus accumbens shell (NAc-S) and its projections to the ventral pallidum (VP) are thought to be critical for stimulus-based decisions. The NAc-S is predominantly composed of spiny projection neurons (SPNs) that express either the dopamine D1 (D1-SPNs) or the dopamine D2 receptor (D2-SPNs). Yet, the role of these two neuronal subpopulations and their inputs to the VP in stimulus-based decisions remains unknown. Here, we used optogenetics in female and male knock-in rats to selectively silence D1-or D2-SPNs and their projections to the VP at a time when the rats were required to use predictive stimuli to choose between two instrumental actions. Silencing either population of NAc-S SPNs disrupted choice. Silencing NAc-S D1-SPNs terminals in the VP also disrupted choice. However, choice was left intact by silencing NAc-S D2-SPNs terminals in the VP. Together, these findings provide novel insights into the cellular mechanisms and circuitry underlying stimulus-based decisions. We discuss how these insights are consistent with a recent model proposing that these decisions are controlled by an opioid-based memory system residing in the NAc-S.

neuroscience↗

bioRxiv2023

Immp2l knockdown increases stimulus-driven instrumental behaviour but does not alter goal-directed learning or neuron density in cortico-striatal circuits in a mouse model of Tourette syndrome and autism spectrum disorder

Cortico-striatal neurocircuits mediate goal-directed and habitual actions which are necessary for adaptive behaviour. It has recently been proposed that some of the core symptoms of autism spectrum disorder (ASD) and Gilles de la Tourette syndrome (GTS), such as tics and repetitive behaviours, may emerge because of imbalances in these neurocircuits. We have recently developed a model of ASD and GTS by knocking down Immp2l, a mitochondrial gene frequently associated with these disorders. The current study sought to determine whether Immp2l knockdown (KD) in male mice alters flexible, goal- or cue-driven behaviour using procedures specifically designed to examine response-outcome and stimulus-response associations, which underlie goal-directed and habitual behaviour, respectively. Whether Immp2l KD alters neuron density in cortico-striatal neurocircuits known to regulate these behaviours was also examined. Immp2l KD mice and wild type-like mice (WT) were trained on Pavlovian and instrumental learning procedures where auditory cues predicted food delivery and lever-press responses earned a food outcome. It was demonstrated that goal-directed learning was not changed for Immp2l KD mice compared to WT mice, as lever-press responses were sensitive to changes in the value of the food outcome, and to contingency reversal and degradation. There was also no difference in the capacity of KD mice to form habitual behaviours compared to WT mice following extending training of the instrumental action. However, Immp2l KD mice were more responsive to auditory stimuli paired with food as indicated by a non-specific increase in lever response rates during Pavlovian-to-instrumental transfer. Finally, there were no alterations to neuron density in striatum or any prefrontal cortex or limbic brain structures examined. Thus, the current study suggests that Immp2l is not necessary for learned maladaptive goal or stimulus driven behaviours in ASD or GTS, but that it may contribute to increased capacity for external stimuli to drive behaviour. Alterations to stimulus-driven behaviour could potentially influence the expression of tics and repetitive behaviours, suggesting that genetic alterations to Immp2l may contribute to these core symptoms in ASD and GTS. Given that this is the first application of this battery of instrumental learning procedures to a mouse model of ASD or GTS, it is an important initial step in determining the contribution of known risk-genes to goal-directed versus habitual behaviours, which should be more broadly applied to other rodent models of ASD and GTS in the future.

neuroscience↗

bioRxiv2019

Goal-directed action transiently depends on action space

Rats use spatiotemporal features of the environment to navigate to a goal, but whether representations of action space are necessary for non-navigational goal-directed actions is unknown. We addressed this question by assessing goal-directed action control across contexts and under hippocampal inactivation and found that such actions do indeed rely on a representation of action space but only immediately after initial acquisition.\n\nOne Sentence SummaryGoal-directed actions depend on a hippocampal representation of action space immediately after initial encoding but not after a delay.

animal behavior and cognition↗