Biology subjects

Laplante, I.

Publications and source records attributed to Laplante, I..

8 recordsLinked to original sources

bioRxiv2025

Basolateral Amygdala Projections to the Prelimbic Cortex Suppress the Motivational Value of Reward-Associated Cues

Reward-associated cues drive reward-seeking behaviours, with different cue types taking on distinct associative meanings. In instrumental settings, discriminative stimuli (DSs) signal when a response will produce reward, while conditioned stimuli (CSs) are paired with reward delivery after responding. Basolateral amygdala (BLA) projections are known to mediate CS-guided reward seeking, but their role in DS-guided behaviour remains unclear despite DSs being uniquely effective in triggering reward seeking. Here, we used optogenetic stimulation of BLA projections to the nucleus accumbens (NAc) core or prelimbic cortex (PrL) to probe their causal involvement in DS- and CS-guided sucrose seeking. Female and male rats learned to lever press during DS+ trials to obtain sucrose paired with a CS+, and to withhold responding during DS-trials where sucrose was unavailable. We then assessed sucrose seeking evoked by response-independent DS+ and CS+ presentations, without sucrose. The DS+ prompted the greatest increases in lever pressing, acting as a strong Pavlovian conditioned excitor. Cue-paired photostimulation of BLA[->]NAc core or BLA[->]PrL projections did not alter this effect. In a test of instrumental responding for conditioned reinforcement, rats lever pressed most for DS+ and CS+ presentations, with no effect of cue-type, indicating that the two cues gained comparable conditioned reinforcing value. While cue-paired photostimulation of BLA[->]NAc core neurons had no impact, photostimulation of BLA[->]PrL projections suppressed instrumental responding for both the DS+ and CS+. These findings reveal the BLA[->]PrL pathway as a key regulator that constrains control over behaviour by reward-associated cues, making them less desirable and reducing their motivational effects.

neuroscience↗

bioRxiv2025

Activation of Infralimbic cortex neurons projecting to the nucleus accumbens shell suppresses discriminative stimulus-triggered relapse to cocaine seeking in rats

Cocaine addiction is marked by high relapse rates, often triggered by drug-associated cues. These cues can be conditioned stimuli (CSs), which occur after drug intake and are paired with drug effects, and discriminative stimuli (DSs), which signal drug availability, regardless of ongoing drug-seeking behaviour. While projections from the infralimbic cortex (IL) to the nucleus accumbens (NAc) shell are known to regulate CS-induced cocaine relapse, their role in DS-triggered relapse is not known. To investigate this, we examined how activating IL[->]NAc shell projections influences relapse driven by DSs and CSs during abstinence from intermittent cocaine use. Female Sprague-Dawley rats received viral-mediated gene expression of excitatory designer receptors exclusively activated by designer drugs in the IL. Rats then self-administered cocaine during 12 intermittent-access sessions (5-min cocaine ON/25-min cocaine OFF, 4h/day). A discrete light (DS+) signalled drug-available periods, while a different light (DS-) signalled drug non-availability. During each DS+ period, cocaine infusions were paired with a compound light-tone (CS+). Four weeks later, rats were tested for cue-induced cocaine seeking following response-independent presentation of DS+, CS+ or both. Immediately prior to testing, rats received intra-NAc shell clozapine N-oxide or aCSF to activate IL terminals. DS+ alone and DS+/CS+ combined triggered greater cocaine seeking than did the CS+. Activation of IL[->]NAc shell projections suppressed relapse behaviour in DS+ and DS+/CS+ conditions. These findings highlight the distinct and powerful influence of DSs on relapse and identify the IL[->]NAc shell circuit as a promising target for relapse prevention.

neuroscience↗

bioRxiv2024

Triggered Temptations: A New Procedure to Compare Reward-Seeking Behaviour Induced by Discriminative and Conditioned Stimuli in Rats

RationaleEnvironmental cues guide animals towards resources vital for survival but can also drive maladaptive reward-seeking behaviours, as in gambling and eating disorders. While conditioned stimuli (CSs) are paired with reward delivery after reward-seeking actions, discriminative stimuli (DSs) signal reward availability independent of behaviour. ObjectiveWe introduce a procedure to compare CS and DS effects on reward-seeking behaviour, in the same subjects within a single session. MethodsFemale and male Sprague-Dawley rats learned to self-administer sucrose. During each session, DS+ trials signaled that lever pressing would produce sucrose paired with a CS+, and DS-trials signaled no sucrose and a CS-. Next, in the absence of sucrose, we assessed the ability of the cues to i) reinforce lever pressing and ii) increase sucrose seeking when presented response-independently. We also assessed the effects of the mGlu2/3 receptor agonist LY379268 and d-amphetamine on cue-induced sucrose seeking. ResultsBy the end of self-administration training, lever pressing peaked during DS+ trials and dropped during DS-trials. The DS+ was a conditioned reinforcer of sucrose seeking in both sexes, whereas the CS+ was more effective in males. Response-independent presentations of the DS+ invigorated sucrose seeking in both sexes, whereas the CS+ was effective only in males. LY379268 suppressed DS+-triggered sucrose seeking in females, with no effect in males. D-amphetamine enhanced sucrose seeking non-specifically across cue conditions in males, with no effect in females. ConclusionsOur new trial-based procedure can be used to identify unique and similar mechanisms underlying DS and CS influences on appetitive behaviour.

neuroscience↗

bioRxiv2024

Activation of Group II Metabotropic Glutamate Receptors in the Basolateral Amygdala Inhibits Reward Seeking Triggered by Discriminative Stimuli

Reward-associated cues are essential in guiding reward-seeking behaviours. These cues include conditioned stimuli (CSs) which occur following seeking actions and indicate reward delivery, and discriminative stimuli (DSs) which occur response-independently and signal reward availability. Metabotropic group II glutamate (mGlu2/3) receptors in the basolateral amygdala (BLA) modulate CS-guided reward seeking; however, their role in DS effects is unknown. We first developed a procedure to assess DS and CS effects on reward seeking in the same subjects within the same test session. Female and male rats first self-administered sucrose during sessions where discriminative stimuli signaled periods of sucrose availability (DS+) and unavailability (DS-). During DS+ presentations, active lever presses produced sucrose paired with a CS+. During DS-presentations, active lever presses produced a CS- and no sucrose. Across 14 sessions, rats learned to load up on sucrose during DS+ presentation and inhibit responding during DS-presentation. We then compared the effects of intra-BLA microinfusions of the mGlu2/3 receptor agonist LY379268 on cue-evoked sucrose seeking during an extinction test (no sucrose) where the DSs and CSs were presented response-independently. Before test, rats received intra-BLA microinjections of artificial cerebrospinal fluid (aCSF) or LY379268. Under aCSF, only the DS+ and DS+CS+ combined triggered increases in reward-seeking behaviour. The CS+ alone was ineffective. Intra-BLA LY379268 reduced sucrose seeking triggered by the DS+ and DS+CS+ combination. Thus, using a new procedure to test reward seeking induced by DSs and CSs, we show that BLA mGlu2/3 receptor activity mediates the conditioned incentive motivational effects of reward predictive DSs.

neuroscience↗

bioRxiv2024

Relapse after intermittent access to cocaine: Discriminative cues more effectively trigger drug seeking than do conditioned cues

When people with drug addiction encounter cues associated with drug use, this can trigger cravings and relapse. These cues can include conditioned stimuli (CSs) signaling drug delivery and discriminative stimuli (DSs) signaling drug availability. Compared to CS effects, DS effects are less explored in preclinical studies on cue-induced relapse. We compared CS and DS effects on reward seeking following abstinence from intermittent-access cocaine (or sucrose) self-administration. During 15-20 intermittent-access sessions, rats self-administered sucrose pellets or i.v. cocaine paired with a light-tone CS. Cocaine/sucrose was available for 5-min (signalled by a light; DS+) and unavailable for 25 min (signalled by different lighting conditions; DS-), and this cycled for 4 h/session. Following abstinence, we measured cocaine/sucrose seeking under extinction triggered by CS and DS presentation, and instrumental responding reinforced by these cues. Across intermittent-access sessions, rats increased lever pressing for cocaine or sucrose during DS+ periods and decreased responding during DS-periods. On days 2 and 21 of abstinence, only presentation of the DS+ or DS+ and CS combined elicited increased cocaine/sucrose-seeking behaviour (i.e., increased active lever presses). Additionally, presenting the DS-alongside the DS+ suppressed the increased cocaine-seeking behaviour otherwise produced by the DS+. Finally, on day 21 of abstinence, rats showed equivalent levels of lever pressing reinforced by the DS+, CS and by the DS+ and CS combined, suggesting comparable conditioned reinforcing value. After intermittent self-administration, cocaine-associated DSs and CSs acquire similar conditioned reinforcing properties, but DSs more effectively trigger increases in drug seeking.

animal behavior and cognition↗

bioRxiv2023

mTORC1-mediated acquisition of reward-related spatial representations by hippocampal somatostatin interneurons

Plasticity of principal cells and inhibitory interneurons underlies hippocampal memory. Bidirectional modulation of somatostatin cell mTORC1 activity, a crucial translational control mechanism in synaptic plasticity, causes parallel changes in hippocampal CA1 somatostatin interneuron (SOM-IN) long-term potentiation and hippocampus-dependent memory, indicating a key role in learning. However, SOM-IN activity changes and behavioral correlates during learning, and the role of mTORC1 in these processes, remain ill-defined. To address these questions, we used two-photon Ca2+ imaging from SOM-INs during a virtual reality goal-directed spatial memory task in head-fixed control mice (SOM-IRES-Cre mice) or in mice with conditional knockout of Rptor (SOM-Rptor-KO mice) to block mTORC1 activity in SOM-INs. We found that control mice learn the task, but SOM-Raptor-KO mice exhibit a deficit. Also, SOM-IN Ca2+ activity became increasingly related to reward localization during learning in control mice but not in SOM-Rptor-KO mice. Four types of SOM-IN activity patterns related to reward location were observed, "reward off sustained", "reward off transient", "reward on sustained" and "reward on transient", and these responses showed global remapping after reward relocation in control but not SOM-Rptor-KO mice. Thus, SOM-INs develop mTORC1-dependent spatial coding related to learning reward localization. This coding may bi-directionally interact with pyramidal cells and other structures to represent and consolidate reward location.

neuroscience↗

bioRxiv2021

Long-term potentiation at pyramidal cell to somatostatin interneuron synapses controls hippocampal network plasticity and memory

Hippocampal somatostatin (SOM) cells are dendrite-projecting inhibitory interneurons. CA1 SOM cells receive major excitatory inputs from pyramidal cells (PC-SOM synapses) which show mGluR1a- and mTORC1-mediated long-term potentiation (LTP). PC-SOM synapse LTP contributes to CA1 network metaplasticity and memory consolidation, but whether it is sufficient to regulate these processes remains unknown. Here we used optogenetic stimulation of CA1 pyramidal cells and whole cell recordings in slices to show that optogenetic theta burst stimulation (TBSopto) produces LTP at PC-SOM synapses. At the network level, we found that TBSopto differentially regulates metaplasticity of pyramidal cell inputs: enhancing LTP at Schaffer collateral synapses and depressing LTP at temporo-ammonic synapses. At the behavioral level, we uncovered that in vivo TBSopto regulates learning-induced LTP at PC-SOM synapses, as well as contextual fear memory. Thus, LTP of PC-SOM synapses is a long-term feedback mechanism controlling pyramidal cell synaptic plasticity, sufficient to regulate memory consolidation.

neuroscience↗

bioRxiv2019

Regulation of hippocampal memory by mTORC1 in somatostatin interneuron

Translational control of long-term synaptic plasticity via Mechanistic Target Of Rapamycin Complex 1 (mTORC1) is crucial for hippocampal learning and memory. The role of mTORC1 is well-characterized in excitatory principal cells but remains largely unaddressed in inhibitory interneurons. Here we used cell type-specific conditional knockout strategies to alter mTORC1 function selectively in somatostatin (SOM) inhibitory interneurons (SOM-INs). We found that up- and down-regulation of SOM-IN mTORC1 activity bi-directionally regulates contextual fear and spatial memory consolidation. Moreover, contextual fear learning induced a metabotropic glutamate receptor type 1 (mGluR1) mediated long-term potentiation (LTP) of excitatory input synapses onto hippocampal SOM-INs, that was dependent on mTORC1. Finally, the induction protocol for mTORC1-mediated late-LTP in SOM-INs regulated Schaffer collateral pathway LTP in pyramidal neurons. Thus, mTORC1 activity in somatostatin interneurons contributes to learning-induced persistent plasticity of their excitatory synaptic inputs and hippocampal memory consolidation, uncovering a role of mTORC1 in inhibitory circuits for memory.

neuroscience↗