Superior Colliculus to VTA pathway controls orienting response and influences social interaction in mice.

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 (VTADA-DLS). While, VTADA-DLS pathway stimulation decreases social interaction, VTADA-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.

NOS1 mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice.

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.

Motor imagery practice benefits during arm immobilization.

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.

Sensorimotor representation and functional motor changes following short-term arm immobilization.

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).