Mini-symposium: Dissecting neural circuits of emotional behaviors

Venue: Centre Broca

9:00 – 11:30

Cyril Herry, Inserm, Neurocentre Magendie

Neuronal representations of defensive states in prefrontal networks

Coping with threatening situations requires both identifying stimuli predicting danger and selecting adaptive behavioural responses in order to survive. The dorsomedial prefrontal cortex (dmPFC) is a critical structure involved in the regulation of threat-related behaviour. Yet, it is still unclear how threat-predicting stimuli and defensive states are associated within prefrontal networks to successfully drive adaptive responses. I will present data collected in mice submitted to a behavioral paradigm combining active and passive defensive behaviors in which we performed extracellular recordings, neuronal decoding approaches, and manipulations of specific interneuronal cell populations. Overall, these data indicate that while the dmPFC encodes dynamically danger and specific threat representations, these specific defensives states are tightly controlled by prefrontal interneuronal activities. Our data unveil the neuronal geometry by which dmPFC networks represent associated threat-predicting stimuli to appropriately drive aversive behaviors.

François Georges, CNRS, IMN

Genetic ablation of a subset of dopaminergic neurons results in  defensive response deficits

Defensive behaviors are essential for survival. The dorsal raphe nucleus (DRN), a neuromodulatory center, plays a key role in processing aversive experiences through its diverse neuronal populations, including dopaminergic neurons (DRN^DA). While the roles of DRN^DA neurons have been studied, their specific contributions to threat evaluation are less understood. Recent research identifies a distinct subset of DRN^DA neurons that express vasoactive intestinal peptide (VIP) and project to the central amygdala (CeA) and the oval nucleus of the bed nucleus of the stria terminalis (ovBNST). Together, these two regions comprise the central extended amygdala, a key network involved in regulating adaptive responses to threats. We hypothesized that DRN_VIP neurons play a pivotal role in coordinating activity between the CeA and ovBNST, thereby influencing defensive response.  To test this, we used a combination of in situ hybridization, immunochemistry, whole-brain mapping, electrophysiology, and cell-specific genetic tools in mice and non-human primates. Our findings reveal that DRN_VIP neurons form a key DRN^DA neuronal subset, uniquely positioned to regulate the central extended amygdala through a feedback loop. These neurons receive inputs from PKCδ neurons in the ovBNST and CeA and send glutamate-releasing projections back to these regions, modulating PKCδ neuron excitability. Selective ablation of DRN_VIP neurons increases activity in both the BNST and CeA, and disrupt defensive behaviors. Together, these findings suggest DRN_VIP neurons orchestrate the central extended amygdala’s role in defensive responses.

Camilla Bellone, Geneva University, Switzerland

Olfactory Tubercle mediates adaptive social behavior through distinct control of threat assessment and memory updating

The ability to dynamically assess and update threat responses based on changing environmental contexts is fundamental for survival. Here, we developed a novel odor-based paradigm to investigate the neural mechanisms underlying social threat processing, where mice first encountered a non-threatening conspecific that subsequently became aggressive. This paradigm allowed us to study how mice assess the threat and update their memories when re-exposed to the aggressor in a non-threatening context. Using a combination of in vivo calcium imaging, chemogenetics, and electrophysiology, we identified the olfactory tubercle (OT) as a key region mediating social threat assessment. While OT activity was not required during the initial aggressive encounter, it proved to be essential during recall, where its inhibition prevented both the expression of avoidance behavior and subsequent memory updating. Importantly, we found that recall induced pathway-specific synaptic plasticity at the basolateral amygdala (BLA) to OT synapses. This plasticity persisted even after behavioral extinction, suggesting a neural substrate for maintaining specific social memories while allowing behavioral flexibility. Given this persistent plasticity, we finally investigated the mechanisms driving avoidance behavior during threat assessment. We found that serotonin release in the OT during recall facilitated avoidance behavior, while its blockade triggered dopamine release and promoted approach behavior, revealing a novel neuromodulatory switch controlling social behavior. Our findings reveal how the OT, through precise neuromodulatory control and synaptic plasticity, orchestrates the dynamic updating of social memories essential for adaptive behavior.

Philip Tovote, Würzburg University, Germany

Integrated defensive state-regulatory mechanisms of the periaqueductal grey

Threatening situations evoke various multi-modal responses that are orchestrated into integrated defensive states. Temporal state dynamics are complex and remain poorly understood. Based on a large dataset of freely moving mice exposed to different threats, we developed a framework for analyses of integrated cardio-behavioral defensive states. In my talk, I will put forth the concept of behaviorally-defined, short-lasting microstates and physiologically-defined, long-lasting macrostates. In addition, I will present evidence for identified brainstem circuit elements mediating micro-and macrostates.

11:00 – 11:30

Coffee break

11:30 – 12:30

Keynote Speaker (Friday seminar)

Nicolas Tritsch – McGill University, Canada

Subsecond dopamine fluctuations do not specify the vigor of ongoing actions

Ever since the discovery that the degeneration of midbrain DA neurons (mDANs) projecting to the striatum underlies bradykinesia (i.e., slowness of movement) in Parkinson’s disease (PD), DA has become synonymous with motor vigor. However, the mechanisms through which DA contributes to the speed and amplitude of individual voluntary movements are still debated. Initial investigations suggested a somewhat slow or permissive role for DA, but recent experiments in rodents proposed a stronger and faster role for DA in the dynamic control of the gain of motor commands. In this presentation, I will describe our latest attempts at better understanding how dopamine contributes to motor vigor through the study of release patterns, lesions, and optogenetic and pharmacological manipulations. Our findings call into question the widely-held view that phasic fluctuations in extracellular dopamine control the vigor of ongoing movements, constraining the kinds of mechanisms and timescales that dopamine likely acts on to modify behavior.

In the frame of Yoni Couderc’s PhD defense

Organizers :

Yoni Couderc & Anna Beyeler
Neurocentre Magendie