Working memory (WM) enables the mammalian brain to temporarily store and manipulate information, supporting cognitive tasks and communication processes. Rather than depending on a single specialized area, WM is thought to operate through a distributed network spanning cortical and subcortical regions. A dedicated WM storage area would likely require broad reciprocal connections with various cortical regions to accommodate the diverse range of information WM retains. The claustrum (CLA), with its extensive bidirectional connections to the neocortex, presents a compelling candidate for such a role. Here, we examined the involvement of the CLA in WM processes by recording CLA neuronal activity in mice engaged in olfactory and tactospatial delayed non-match-to-sample WM tasks. We identified cue-selective and delay-specific neurons in the CLA that maintained activity for tens of seconds after the stimulus presentation ended. Additionally, population activity in the CLA allowed for decoding of cue identity post-stimulus, although this signal gradually declined over time, aligning with animal behavior. Remarkably, both chemo- and optogenetic inhibition of CLA neurons severely impaired WM performance across multiple types of stored information, highlighting the CLA's critical role during both cue encoding, delay periods, and target comparison phases. These findings challenge the view that no single brain area is essential for WM storage and support a role for the CLA as an essential WM storage hub. ### Competing Interest Statement The authors have declared no competing interest.

The nitric oxide (NO) signaling pathway in hypothalamic neurons plays a key role in the regulation of the secretion of gonadotropin-releasing hormone (GnRH), which is crucial for reproduction. We hypothesized that a disruption of neuronal NO synthase (NOS1) activity underlies some forms of hypogonadotropic hypogonadism. Whole-exome sequencing was performed on a cohort of 341 probands with congenital hypogonadotropic hypogonadism to identify ultrarare variants in NOS1 . The activity of the identified NOS1 mutant proteins was assessed by their ability to promote nitrite and cGMP production in vitro. In addition, physiological and pharmacological characterization was carried out in a Nos1 -deficient mouse model. We identified five heterozygous NOS1 loss-of-function mutations in six probands with congenital hypogonadotropic hypogonadism (2%), who displayed additional phenotypes including anosmia, hearing loss, and intellectual disability. NOS1 was found to be transiently expressed by GnRH neurons in the nose of both humans and mice, and Nos1 deficiency in mice resulted in dose-dependent defects in sexual maturation as well as in olfaction, hearing, and cognition. The pharmacological inhibition of NO production in postnatal mice revealed a critical time window during which Nos1 activity shaped minipuberty and sexual maturation. Inhaled NO treatment at minipuberty rescued both reproductive and behavioral phenotypes in Nos1 -deficient mice. In summary, lack of NOS1 activity led to GnRH deficiency associated with sensory and intellectual comorbidities in humans and mice. NO treatment during minipuberty reversed deficits in sexual maturation, olfaction, and cognition in Nos1 mutant mice, suggesting a potential therapy for humans with NO deficiency.

Social behaviours characterize cooperative, mutualistic, aggressive or parental interactions that occur among conspecifics. Although the Ventral Tegmental Area (VTA) has been identified as a key substrate for social behaviours, the input and output pathways dedicated to specific aspects of conspecific interaction remain understudied. Here, in male mice, we investigated the activity and function of two distinct VTA inputs from superior colliculus (SC-VTA) and medial prefrontal cortex (mPFC-VTA). We observed that SC-VTA neurons display social interaction anticipatory calcium activity, which correlates with orienting responses towards an unfamiliar conspecific. In contrast, mPFC-VTA neuron population activity increases after initiation of the social contact. While protracted phasic stimulation of SC-VTA pathway promotes head/body movements and decreases social interaction, inhibition of this pathway increases social interaction. Here, we found that SC afferents mainly target a subpopulation of dorsolateral striatum (DLS)-projecting VTA dopamine (DA) neurons (VTA DA -DLS). While, VTA DA -DLS pathway stimulation decreases social interaction, VTA DA -Nucleus Accumbens stimulation promotes it. Altogether, these data support a model by which at least two largely anatomically distinct VTA sub-circuits oppositely control distinct aspects of social behaviour.

Motor imagery (MI) is known to engage motor networks and is increasingly used as a relevant strategy in functional rehabilitation following immobilization, whereas its effects when applied during immobilization remain underexplored. Here, we hypothesized that MI practice during 11 h of arm-immobilization prevents immobilization-related changes at the sensorimotor and cortical representations of hand, as well as on sleep features. Fourteen participants were tested after a normal day (without immobilization), followed by two 11-h periods of immobilization, either with concomitant MI treatment or control tasks, one week apart. At the end of each condition, participants were tested on a hand laterality judgment task, then underwent transcranial magnetic stimulation to measure cortical excitability of the primary motor cortices (M1), followed by a night of sleep during which polysomnography data was recorded. We show that MI treatment applied during arm immobilization had beneficial effects on (1) the sensorimotor representation of hands, (2) the cortical excitability over M1 contralateral to arm-immobilization, and (3) sleep spindles over both M1s during the post-immobilization night. Furthermore, (4) the time spent in REM sleep was significantly longer, following the MI treatment. Altogether, these results support that implementing MI during immobilization may limit deleterious effects of limb disuse, at several levels of sensorimotor functioning.

SUMMARYIn various mental disorders, dysfunction of the prefrontal cortex contributes to cognitive deficits. Here we studied how the claustrum (CLA), a nucleus sharing reciprocal connections with the cortex, may participate in these cognitive impairments. We show that specific ensembles of CLA and of medial prefrontal cortex (mPFC) neurons are activated during a task requiring cognitive control such as attentional set-shifting, i.e. the ability to shift attention towards newly relevant stimulus-reward associations while disengaging from irrelevant ones. CLA neurons exert a direct excitatory input on mPFC pyramidal cells, and chemogenetic inhibition of CLA neurons suppresses the formation of specific mPFC assemblies during attentional set-shifting. Furthermore, impairing the recruitment of specific CLA assemblies through opto/chemogenetic manipulations prevents attentional set-shifting. In conclusion, we propose that the CLA controls the reorganization of mPFC ensembles to enable attentional set-shifting, emphasizing a potential role of the CLA-mPFC network in attentional dysfunctions.

Social behaviours characterize cooperative, mutualistic aggressive or parental interactions that occurs among conspecifics. Although several neuronal substrates of social behaviour have been identified, whether defined circuits are dedicated to specific aspect of conspecific interaction is still an open question. Ventral Tegmental Area (VTA) contributes to the rewarding properties of conspecific interaction. However, how information related to conspecifics are conveyed to the VTA is still largely unknown. In this study, we identified a population of Superior Colliculus (SC) neurons projecting to the VTA which increase their activity before conspecific interaction and control orienting response towards unfamiliar conspecifics. Finally, we show that SC inputs target a subpopulation of Dopamine (DA) neurons within the VTA that in turn project to dorsolateral striatum (DLS). Our work supports the hypothesis that specialized sub-circuits are dedicated to process different aspect of social interaction. ### Competing Interest Statement The authors have declared no competing interest.

The claustrum is a brain structure that is identified in most mammalian species but little experimental evidence supports its hypothetical functions, resulting from the difficulty to specifically manipulate claustral activities without affecting surrounding brain areas. The first study thus aimed to relate better the physiology of the network of claustral neurons to behavior, and investigate its functional role. We characterized a group of claustral neurons during several behaviors by microendoscope. Given the importance of the contribution of the claustrum to the cognitive task requiring attentional set shifting, the second study aimed to assess the ability of attentional set shifting in heterozygous Nr4a2 deletion mice which a genetic mouse model of schizophrenia, and to investigate the involvement of the claustrum in the pathology. Our findings propose that the claustrum-medial prefrontal cortex network controls attentional set shifting and suggest the potential role of the network in attention dysfunctions observed in schizophrenia.

Limb immobilization paradigms are increasingly used to investigate changes in brain plasticity and support potential rehabilitation techniques that might help counteract motor impairments. Yet, it remains unclear how unilateral arm immobilization may influence the sensorimotor representation and functional output for both arms. Using a randomized crossover design, 14 participants underwent a baseline test, followed by two experimental conditions separated by 1 week: a right (dominant) arm immobilization phase over a period of 8 hr and a no-immobilization (or control) phase also lasting 8 hr. Before and after each condition, participants were tested on a hand laterality judgment task to assess changes in sensorimotor representation of the hands, followed by an out-and-back reaching motor task measuring changes in spatiotemporal components of motor actions. Data from the hand laterality judgment task revealed that participants were faster at identifying right-hand pictures after the control phase, but such improvement was not observed after the immobilization phase, with no effect of immobilization for pictures depicting the overused left hand. Results from the reaching motor task revealed that the right-arm movement planning component was altered after immobilization, whereas there was no effect for the overused left arm. Altogether, these findings demonstrate that an 8-hr period of unilateral immobilization affects sensorimotor representation and functions of the corresponding limb, but not of the overused, nonimmobilized hand. (PsycINFO Database Record (c) 2018 APA, all rights reserved).