Opposing Roles of the Dorsolateral and Dorsomedial Striatum in the Acquisition of Skilled Action Sequencing in Rats.

The shift in control from dorsomedial to dorsolateral striatum during skill and habit formation has been well established, but whether striatal subregions orchestrate this shift cooperatively or competitively remains unclear. Cortical inputs have also been implicated in the shift toward automaticity, but it is unknown whether they mirror their downstream striatal targets across this transition. We addressed these questions using a five step heterogeneous action sequencing task in male rats that is optimally performed by automated chains of actions. By optimizing automatic habitual responding, we discovered that loss of function in the dorsomedial striatum accelerated sequence acquisition. In contrast, loss of function in the dorsolateral striatum impeded acquisition of sequencing, demonstrating functional opposition within the striatum. Unexpectedly, the mPFC was not involved; however, the lateral orbitofrontal cortex was critical. These results shift current theories about striatal control of behavior to a model of competitive opposition, where the dorsomedial striatum interferes with the development of dorsolateral-striatum dependent behavior.SIGNIFICANCE STATEMENT We provide the most direct evidence to date that the dorsomedial and dorsolateral striatum compete for control in the acquisition of habitual action sequences. The dorsolateral striatum was critical for sequencing behavior, but loss of dorsomedial striatum function enhanced acquisition. In addition, we found that the mPFC was not required for the formation of automated actions. Using a task that optimizes habitual responding, we demonstrate that the arbitration of dorsomedial and dorsolateral control is not modulated by medial prefrontal cortical activity. However, we find evidence for the role of the lateral orbitofrontal cortex in action sequencing. These results have implications for our understanding of how habits and skills form.

Oxytocin and vasopressin inhibit hyper-aggressive behaviour in socially isolated mice.

Despite the high prevalence of aggression across a wide range of disorders, there is a severe lack of pharmacological treatments. Recent rodent studies have shown both centrally and peripherally administered oxytocin is effective in reducing territorial aggression, an adaptive form of aggression not reflective of pathological hyper-aggression. The current study tested i.p. administered oxytocin and vasopressin in a model of non-territorial hyper-aggression and examined the involvement of oxytocin receptors (OXTR) and vasopressin V1a receptors (V1aR). Male Swiss mice (N = 160) were either socially isolated or group housed for 6 weeks prior to the commencement of testing; wherein two unfamiliar weight and condition matched mice were placed into a neutral context for 10 min. Socially isolated mice exhibited heightened aggression that was powerfully and dose-dependently inhibited by oxytocin and vasopressin and that was accompanied by dose-dependent increases in close social contact (huddling) and grooming. These anti-aggressive effects of oxytocin were blocked by pre-treatment with a higher dose of selective V1aR antagonist SR49059 (20 mg/kg i.p.), but not a lower dose of SR49059 (5 mg/kg i.p.) or selective OXTR antagonist L-368,899 (10 mg/kg i.p.). This is consistent with a growing number of studies linking a range of effects of exogenous oxytocin to actions at the V1a receptor. Interestingly, the highest dose of the OXTR agonist TGOT (10 mg/kg) also reduced isolation-induced aggression. These results suggest that while activation of the V1a receptor appears critical for the anti-aggressive effects of oxytocin, activation of the oxytocin receptor cannot be excluded. This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity.'

Developmental Vitamin D Deficiency Produces Behavioral Phenotypes of Relevance to Autism in an Animal Model.

Emerging evidence suggests that gestational or developmental vitamin D (DVD) deficiency is associated with an increased risk of autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder characterized by impairments in social interaction, lack of verbal and non-verbal communications, stereotyped repetitive behaviors and hyper-activities. There are several other clinical features that are commonly comorbid with ASD, including olfactory impairments, anxiety and delays in motor development. Here we investigate these features in an animal model related to ASD-the DVD-deficient rat. Compared to controls, both DVD-deficient male and female pups show altered ultrasonic vocalizations and stereotyped repetitive behavior. Further, the DVD-deficient animals had delayed motor development and impaired motor control. Adolescent DVD-deficient animals had impaired reciprocal social interaction, while as adults, these animals were hyperactive. The DVD-deficient model is associated with a range of behavioral features of interest to ASD.