Behavioral inflexibility through overtraining is mediated by reduced mGluR1/5 signaling capacity in the dorsolateral striatum.

The control of instrumental actions engages distinct behavioral strategies whose contributions are regulated with experience. Instrumental performance, which depends on the causal relationship between actions and their outcomes (A-O), relies on flexible, goal-directed control of behavior. Actions can become less sensitive to changes in action-outcome (A-O) contingencies with repetition, resulting in more inflexible, habitual behaviors.

Holistic Motor Control of Zebra Finch Song Syllable Sequences.

How brain circuits are organized to skillfully produce learned sequences of behaviors is still poorly understood. Here, we functionally examine how the 'cortical' song premotor region HVC, which is necessary for zebra finch song, controls the sequential production of learned song syllables. We find that HVC can generate the complete sequence of learned song syllables independently of its main synaptic input pathways.

Synaptic connectivity of sensorimotor circuits for vocal imitation in the songbird.

Sensorimotor computations for learning and behavior rely on precise patterns of synaptic connectivity. Yet, we typically lack the synaptic wiring diagrams for long-range connections between sensory and motor circuits in the brain. Here, we provide the synaptic wiring diagram for sensorimotor circuits involved in learning and production of male zebra finch song, a natural and ethologically relevant behavior.

Acute Effects of the Psychedelic Phenethylamine 25I-NBOMe in C57BL/6J Male Mice.

25I-NBOMe (4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl) phenethylamine) is a synthetic psychedelic compound abused for its ambiguous legal state as a counterfeit lysergic acid diethylamide (LSD). 25I-NBOMe acts as a selective agonist of 5HT receptors leading to hallucinations, intoxications, and fatalities. Here, we assessed the rewarding properties of 25I-NBOMe and its behavioral and neurotoxic acute effects on the central nervous system of C57BL/6J mice.

Bidirectional synaptic changes in deep and superficial hippocampal neurons following in vivo activity.

Neuronal activity during experience is thought to induce plastic changes within the hippocampal network that underlie memory formation, although the extent and details of such changes in vivo remain unclear. Here, we employed a temporally precise marker of neuronal activity, CaMPARI2, to label active CA1 hippocampal neurons in vivo, followed by immediate acute slice preparation and electrophysiological quantification of synaptic properties. Recently active neurons in the superficial sublayer of stratum pyramidale displayed larger post-synaptic responses at excitatory synapses from area CA3, with no change in pre-synaptic release probability.

Neural circuits: How the songbird brain orchestrates courtship displays.

Volitional production of complex behaviors can be motivated by intrinsic rewards and also by extrinsic cues, like social engagement. A new study has revealed the neural circuit permitting social motivation to release multi-component courtship behaviors in a songbird, specifically the zebra finch.

Stress undermines reward-guided cognitive performance through synaptic depression in the lateral habenula.

Weighing alternatives during reward pursuit is a vital cognitive computation that, when disrupted by stress, yields aspects of neuropsychiatric disorders. To examine the neural mechanisms underlying these phenomena, we employed a behavioral task in which mice were confronted by a reward and its omission (i.e.

Memory circuits for vocal imitation.

Many complex behaviors exhibited by social species are first learned by imitating the behavior of other more experienced individuals. Speech and language are the most widely appreciated behaviors learned in this way. Vocal imitation in songbirds is perhaps the best studied socially transmitted behavior, and research over the past few years has begun to crack the circuit mechanisms for how songbirds learn from vocal models.

Morphine withdrawal recruits lateral habenula cytokine signaling to reduce synaptic excitation and sociability.

The lateral habenula encodes aversive stimuli contributing to negative emotional states during drug withdrawal. Here we report that morphine withdrawal in mice leads to microglia adaptations and diminishes glutamatergic transmission onto raphe-projecting lateral habenula neurons. Chemogenetic inhibition of this circuit promotes morphine withdrawal-like social deficits.

Opposite responses to aversive stimuli in lateral habenula neurons.

Appropriate behavioural strategies to cope with unexpected salient stimuli require synergistic neuronal responses in diverse brain regions. Among them, the epithalamic lateral habenula (LHb) plays a pivotal role in processing salient stimuli of aversive valence. Integrated in the complex motivational circuit, LHb neurons are indeed excited by aversive stimuli, including footshock (Fs).

Punishment-Predictive Cues Guide Avoidance through Potentiation of Hypothalamus-to-Habenula Synapses.

Throughout life, individuals learn to predict a punishment via its association with sensory stimuli. This process ultimately prompts goal-directed actions to prevent the danger, a behavior defined as avoidance. Neurons in the lateral habenula (LHb) respond to aversive events as well as to environmental cues predicting them, supporting LHb contribution to cue-punishment association.

Adult Cellular Neuroadaptations Induced by Adolescent THC Exposure in Female Rats Are Rescued by Enhancing Anandamide Signaling.

Background: In rodent models, chronic exposure to cannabis' psychoactive ingredient, Δ9-tetrahydrocannabinol, during adolescence leads to abnormal behavior in adulthood. In female rats, this maladaptive behavior is characterized by endophenotypes for depressive-like and psychotic-like disorders as well as cognitive deficits. We recently reported that most depressive-like behaviors triggered by adolescent Δ9-tetrahydrocannabinol exposure can be rescued by manipulating endocannabinoid signaling in adulthood with the anandamide-inactivating enzyme FAAH inhibitor, URB597.

Serotonergic Signaling Controls Input-Specific Synaptic Plasticity at Striatal Circuits.

Monoaminergic modulation of cortical and thalamic inputs to the dorsal striatum (DS) is crucial for reward-based learning and action control. While dopamine has been extensively investigated in this context, the synaptic effects of serotonin (5-HT) have been largely unexplored. Here, we investigated how serotonergic signaling affects associative plasticity at glutamatergic synapses on the striatal projection neurons of the direct pathway (dSPNs).

Internalization of Carbon Nano-onions by Hippocampal Cells Preserves Neuronal Circuit Function and Recognition Memory.

One area where nanomedicine may offer superior performances and efficacy compared to current strategies is in the diagnosis and treatment of central nervous system (CNS) diseases. However, the application of nanomaterials in such complex arenas is still in its infancy and an optimal vector for the therapy of CNS diseases has not been identified. Graphitic carbon nano-onions (CNOs) represent a class of carbon nanomaterials that shows promising potential for biomedical purposes.

cJun N-terminal kinase (JNK) mediates cortico-striatal signaling in a model of Parkinson's disease.

The cJun N-terminal kinase (JNK) signaling pathway has been extensively studied with regard to its involvement in neurodegenerative processes, but little is known about its functions in neurotransmission. In a mouse model of Parkinson's disease (PD), we show that the pharmacological activation of dopamine D1 receptors (D1R) produces a large increase in JNK phosphorylation. This effect is secondary to dopamine depletion, and is restricted to the striatal projection neurons that innervate directly the output structures of the basal ganglia (dSPN).

Inhibition of IL-1β Signaling Normalizes NMDA-Dependent Neurotransmission and Reduces Seizure Susceptibility in a Mouse Model of Creutzfeldt-Jakob Disease.

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disorder caused by prion protein (PrP) misfolding, clinically recognized by cognitive and motor deficits, electroencephalographic abnormalities, and seizures. Its neurophysiological bases are not known. To assess the potential involvement of NMDA receptor (NMDAR) dysfunction, we analyzed NMDA-dependent synaptic plasticity in hippocampal slices from Tg(CJD) mice, which model a genetic form of CJD.

Aversive stimuli drive hypothalamus-to-habenula excitation to promote escape behavior.

A sudden aversive event produces escape behaviors, an innate response essential for survival in virtually all-animal species. Nuclei including the lateral habenula (LHb), the lateral hypothalamus (LH), and the midbrain are not only reciprocally connected, but also respond to negative events contributing to goal-directed behaviors. However, whether aversion encoding requires these neural circuits to ultimately prompt escape behaviors remains unclear.

Neural circuit adaptations during drug withdrawal - Spotlight on the lateral habenula.

Withdrawal after drug intake triggers a wealth of affective states including negative feelings reminiscent of depressive symptoms. This negative state can ultimately be crucial for relapse, a hallmark of addiction. Adaptations in a wide number of neuronal circuits underlie aspects of drug withdrawal, however causality between cellular modifications within these systems and precise behavioral phenotypes remains poorly described.

Footshock-induced plasticity of GABA signalling in the lateral habenula requires dopamine and glucocorticoid receptors.

The activity of lateral habenula (LHb) represents a substrate for the encoding of negative-valenced events. The exposure to aversive stimuli in naïve mice is sufficient to trigger a reduction in GABA -mediated signaling in the LHb. This is ultimately instrumental for the hyperactivity of LHb neurons and for the establishment of depressive-like phenotypes.

Carbon Nanomaterials Interfacing with Neurons: An In vivo Perspective.

Developing new tools that outperform current state of the art technologies for imaging, drug delivery or electrical sensing in neuronal tissues is one of the great challenges in neurosciences. Investigations into the potential use of carbon nanomaterials for such applications started about two decades ago. Since then, numerous in vitro studies have examined interactions between these nanomaterials and neurons, either by evaluating their compatibility, as vectors for drug delivery, or for their potential use in electric activity sensing and manipulation.

Coordinated Regulation of Synaptic Plasticity at Striatopallidal and Striatonigral Neurons Orchestrates Motor Control.

The basal ganglia play a critical role in shaping motor behavior. For this function, the activity of medium spiny neurons (MSNs) of the striatonigral and striatopallidal pathways must be integrated. It remains unclear whether the activity of the two pathways is primarily coordinated by synaptic plasticity mechanisms.

Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.

Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means.

SK channel modulation rescues striatal plasticity and control over habit in cannabinoid tolerance.

Endocannabinoids (eCBs) regulate neuronal activity in the dorso-lateral striatum (DLS), a brain region that is involved in habitual behaviors. How synaptic eCB signaling contributes to habitual behaviors under physiological and pathological conditions remains unclear. Using a mouse model of cannabinoid tolerance, we found that persistent activation of the eCB pathway impaired eCB-mediated long-term depression (LTD) and synaptic depotentiation in the DLS.

The puzzle box as a simple and efficient behavioral test for exploring impairments of general cognition and executive functions in mouse models of schizophrenia.

Deficits in executive functions are key features of schizophrenia. Rodent behavioral paradigms used so far to find animal correlates of such deficits require extensive effort and time. The puzzle box is a problem-solving test in which mice are required to complete escape tasks of increasing difficulty within a limited amount of time.