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Cocaine is known to influence the synaptic plasticity of dopaminergic neurons in the ventral tegmental area (VTA). Contrary to the earlier studies, Mameli et al. find that cocaine treatment can reduce synaptic NMDA receptor currents while increasing the synaptic insertion of calcium-permeable AMPA receptors. Cocaine treatment also reversed the rule of spiking timing–dependent plasticity in the VTA.

The vesicular transporter VGAT controls GABA vesicle filling at inhibitory terminals. Here Meye et al. show that cocaine withdrawal reduces VGAT at synapses from pallidum to lateral habenula, thereby decreasing inhibitory transmission. This GABAergic synaptic plasticity is crucial for behaviors modeling cocaine-evoked aversive states and stress-induced relapse.

Dysregulated GABA-GIRK signaling drives lateral habenula hyperactivity in mouse models of depression. Restoring GABA-GIRK signaling by treatment with a PP2A inhibitor alleviates depression-like phenotypes.

Tracking of astrocytes dynamics in habenula reveals their contribution to behavioral transitions across species.

Early-life stress primes depression in adulthood. This study shows that early maternal separation leads to lateral habenula (LHb) hyperactivity and causes depressive-like phenotypes, the latter being reversible when LHb hyperactivity is reduced chemogenetically or through deep-brain stimulation.

Addictive substances hijack the reward system partly via synaptic plasticity onto dopamine neurons. Cadherins may contribute to cocaine-evoked adaptations, supporting the notion that drug addiction is a synaptic disease.

The authors show that decreased synaptic efficacy onto raphe-projecting lateral habenula neurons supports opiate withdrawal-induced sociability deficits, and they demonstrate a role for TNF-α signaling in this process.

The role of lactate in the control of microglial function remains poorly investigated. Here, the authors show that lactate promotes lysosomal acidification in microglia, and that mice lacking the lactate transporter MCT4 in these cells display defective brain development and anxiety-like behavior.

A subpopulation of astrocytes selectively expresses synaptic-like glutamate-release machinery, actively secretes the transmitter and is localized to discrete sites in the hippocampus.

In humans, copy-number variants of the CYFIP1 gene have been associated with autism spectrum disorders and schizophrenia. Here, the authors characterize Cyfip1-heterozygous mice, revealing that they display deficits in brain white matter structure and functional connectivity along with abnormal behaviours.

Cutando and colleagues show that changes in D2 dopamine receptor levels in cerebellar Purkinje cells alter sociability and preference for social novelty without affecting motor functions.

The authors combine electrophysiology and behavioral assays to show that the duration of cocaine-induced synaptic plasticity in the VTA of mice is gated by mGluR1. The lack of mGluR1 in vivo made VTA potentiation persistent and led to synaptic plasticity in the NAc, which is important for relapse.

Cocaine can easily cross the placental and fetal blood-brain barrier, and in utero exposure to cocaine can cause lasting behavioral changes in postnatal periods. Here, Bellone et al. studied the physiological and circuit level mechanism behind the consequence of in utero cocaine exposure and found a postnatal synaptic maturation defect of excitatory input to the dopaminergic neurons in the ventral tegmental area of mice. In particular, they found that late embryonic in utero cocaine exposure causes a delay in AMPAR/NMDAR switch in early postnatal mouse brain.

This study shows that cocaine strengthens glutamatergic transmission, reduces K⁺ channel function and drives hyperexcitability in lateral habenula neurons projecting to the rostromedial tegmental nucleus. The authors also show that GluA1 trafficking mediates these cellular modifications and is instrumental in a drug-mediated depressive-like phenotype.