habenula

Astroglial modulation of the antidepressant action of deep brain and bright light stimulation

Even if major depression is now the most common of psychiatric disorders, successful antidepressant treatments are still difficult to achieve. Therefore, a better understanding of the mechanisms of action of current antidepressant treatments is needed to ultimately identify new targets and enhance beneficial effects. Given the intimate relationships between astrocytes and neurons at synapses and the ability of astrocytes to "sense" neuronal communication and release gliotransmitters, an attractive hypothesis is emerging stating that the effects of antidepressants on brain function could be, at least in part, modulated by direct influences of astrocytes on neuronal networks. We will present two preclinical studies revealing a permissive role of glia in the antidepressant response: i) Control of the antidepressant-like effects of rat prefrontal cortex Deep Brain Stimulation (DBS) by astroglia, ii) Modulation of antidepressant efficacy of Bright Light Stimulation (BLS) by lateral habenula astroglia. Therefore, it is proposed that an unaltered neuronal-glial system constitutes a major prerequisite to optimize antidepressant efficacy of DBS or BLS. Collectively, these results pave also the way to the development of safer and more effective antidepressant strategies.

Neural circuits for novel choices and for choice speed and accuracy changes in macaques

While most experimental tasks aim at isolating simple cognitive processes to study their neural bases, naturalistic behaviour is often complex and multidimensional. I will present two studies revealing previously uncharacterised neural circuits for decision-making in macaques. This was possible thanks to innovative experimental tasks eliciting sophisticated behaviour, bridging the human and non-human primate research traditions. Firstly, I will describe a specialised medial frontal circuit for novel choice in macaques. Traditionally, monkeys receive extensive training before neural data can be acquired, while a hallmark of human cognition is the ability to act in novel situations. I will show how this medial frontal circuit can combine the values of multiple attributes for each available novel item on-the-fly to enable efficient novel choices. This integration process is associated with a hexagonal symmetry pattern in the BOLD response, consistent with a grid-like representation of the space of all available options. We prove the causal role played by this circuit by showing that focussed transcranial ultrasound neuromodulation impairs optimal choice based on attribute integration and forces the subjects to default to a simpler heuristic decision strategy. Secondly, I will present an ongoing project addressing the neural mechanisms driving behaviour shifts during an evidence accumulation task that requires subjects to trade speed for accuracy. While perceptual decision-making in general has been thoroughly studied, both cognitively and neurally, the reasons why speed and/or accuracy are adjusted, and the associated neural mechanisms, have received little attention. We describe two orthogonal dimensions in which behaviour can vary (traditional speed-accuracy trade-off and efficiency) and we uncover independent neural circuits concerned with changes in strategy and fluctuations in the engagement level. The former involves the frontopolar cortex, while the latter is associated with the insula and a network of subcortical structures including the habenula.

Habenular synaptic strength and neuronal dynamics for approach-avoidance behaviours

Function and development of neuronal ensembles in zebrafish habenula

Habenular circuits in deciding actions

Recurrent network models of adaptive and maladaptive learning

During periods of persistent and inescapable stress, animals can switch from active to passive coping strategies to manage effort-expenditure. Such normally adaptive behavioural state transitions can become maladaptive in disorders such as depression. We developed a new class of multi-region recurrent neural network (RNN) models to infer brain-wide interactions driving such maladaptive behaviour. The models were trained to match experimental data across two levels simultaneously: brain-wide neural dynamics from 10-40,000 neurons and the realtime behaviour of the fish. Analysis of the trained RNN models revealed a specific change in inter-area connectivity between the habenula (Hb) and raphe nucleus during the transition into passivity. We then characterized the multi-region neural dynamics underlying this transition. Using the interaction weights derived from the RNN models, we calculated the input currents from different brain regions to each Hb neuron. We then computed neural manifolds spanning these input currents across all Hb neurons to define subspaces within the Hb activity that captured communication with each other brain region independently. At the onset of stress, there was an immediate response within the Hb/raphe subspace alone. However, RNN models identified no early or fast-timescale change in the strengths of interactions between these regions. As the animal lapsed into passivity, the responses within the Hb/raphe subspace decreased, accompanied by a concomitant change in the interactions between the raphe and Hb inferred from the RNN weights. This innovative combination of network modeling and neural dynamics analysis points to dual mechanisms with distinct timescales driving the behavioural state transition: early response to stress is mediated by reshaping the neural dynamics within a preserved network architecture, while long-term state changes correspond to altered connectivity between neural ensembles in distinct brain regions.

Integrating information and reward into subjective value: humans, monkeys, and the lateral habenula

COSYNE 2022

Integrating information and reward into subjective value: humans, monkeys, and the lateral habenula

COSYNE 2022

Acetylcholine and Lateral Habenula partnership in shaping punishment anticipation

Age-dependent dynamics in acute and chronic stress-induced FOSB/∆FOSB content in the extended amygdala, hypothalamic paraventricular, habenular, centrally-projecting Edinger-Westphal and dorsal raphe nuclei in male rats

Characterization of a habenula-driven serotonergic recurrent inhibitory network in dorsal raphe nucleus

Experience-dependent plasticity of burst activity in lateral habenula neurons

An extended amygdala-habenula circuit for parental behaviours

Functional hemispheric asymmetry of medial habenula-to-interpeduncular nucleus synapses and its implications in emotion-related behaviors in mice

Including the lateral habenula in the stress-related functional network

Induction of phasic neurotransmitter release via presynaptic GABAB receptors on medial habenula terminals

Inhibition mediated by group III mGluRs regulates habenular activity and defensive behaviors

Molecular characterization of habenula nuclei in a genetic rat model of drug-resistant depression

Responses of lateral habenula neurons to an aversive stimulus across alternating brain states of urethane anaesthetised rat

Role of a hypothalamus-habenula circuit in acupuncture inhibition of cocaine addiction-like behaviors

Role of a lateral hypothalamus-lateral habenula pathway in cocaine-induced psychomotor responses

Sequential neurogenesis in zebrafish habenula give rise to distinct functional microcircuits with distinct computational properties

Ventral Pallidum activation differentially modulates the Mediodorsal Thalamus and the Lateral Habenula of rats

Comparative analysis of the molecular, spatial, and functional domains of vertebrate habenula

FENS Forum 2024

Distinct hypothalamus-habenula circuits govern risk preference

FENS Forum 2024

Dynamics of neuronal and non-neuronal cells in lateral habenula in response to threats

FENS Forum 2024

Functional hemispheric asymmetry of medial habenula is associated with fear expression via modulation of GABAB receptor signaling in mice

FENS Forum 2024

GABAB receptors induce phasic release from medial habenula terminals through activity-dependent recruitment of release-ready vesicles

FENS Forum 2024

Longitudinal assessment of behaviour and neuronal activity in the lateral habenula in a mouse model of depression

FENS Forum 2024

Nigroincertal activation engages lateral habenula and periaqueductal gray

FENS Forum 2024

Plasticity in the lateral habenula after adult-newborn interactions

FENS Forum 2024

Sequential neurogenesis in zebrafish habenula gives rise to distinct functional microcircuits

FENS Forum 2024