Multiple cortical areas contribute to visual processing in mice. However, the functional organization and development of higher visual areas are unclear. Here, we used intrinsic signal optical imaging and 2-photon calcium imaging to map visual responses in adult and developing mice. We found that visually driven activity was well-correlated among higher visual areas within two distinct subnetworks resembling the dorsal and ventral visual streams. Visual response magnitude in dorsal stream areas slowly increased over the first two weeks of visual experience. By contrast, ventral stream areas exhibited strong responses shortly after eye opening. Neurons in a dorsal stream area showed little change in their tuning sharpness to oriented gratings while those in a ventral stream area increased stimulus selectivity and expanded their receptive fields significantly. Together, these findings provide a functional basis for grouping subnetworks of mouse visual areas and revealed stream differences in the development of receptive field properties.

Global motion perception is a function of higher, or extrastriate, visual system circuitry. These circuits can be engaged in visually driven navigation, a behavior at which mice are adept. However, the properties of global motion perception in mice are unclear. Therefore, we developed a touchscreen-based, two-alternative forced choice (2AFC) task to explore global motion detection in mice using random dot kinematograms (RDK). Performance data was used to compute coherence thresholds for global motion perception. The touchscreen-based task allowed for parallel training and testing with multiple chambers and minimal experimenter intervention with mice performing hundreds of trials per session. Parameters of the random dot kinematograms, including dot size, lifetime, and speed, were tested. Mice learned to discriminate kinematograms whose median motion direction differed by 90 degrees in 7-24 days after a 10-14 day pre-training period. The average coherence threshold (measured at 70% correct) in mice for this task was 22 ± 5%, with a dot diameter of 3.88 mm and speed of 58.2 mm/second. Our results confirm the ability of mice to perform global motion discriminations, and the touchscreen assay provides a flexible, automated, and relatively high throughput method with which to probe complex visual function in mice.

The cycle of chronic cocaine (CC) use and withdrawal results in increased anxiety, depression and disrupted stress-responsiveness. Oxytocin and corticosterone (CORT) interact to mediate hormonal stress responses and can be altered by cocaine use. These neuroendocrine signals play important regulatory roles in a variety of social behaviours, specifically during the postpartum period, and are sensitive to disruption by CC exposure in both clinical settings and preclinical models. To determine whether CC exposure during pregnancy affected behavioural and hormonal stress response in the early postpartum period in a rodent model, Sprague-Dawley rats were administered cocaine daily (30 mg/kg) throughout gestation (days 1–20). Open field test (OFT) and forced swim test (FST) behaviours were measured on postpartum day 5. Plasma CORT concentrations were measured prior to and following testing throughout the test day, while plasma and brain oxytocin concentrations were measured post-testing only. Results indicated increased CORT response following the OFT in CC-treated dams (p≤ 0.05). CC-treated dams also exhibited altered FST behaviour (p≤ 0.05), suggesting abnormal stress responsiveness. Peripheral, but not central, oxytocin levels were increased by cocaine treatment (p≤ 0.05). Peripheral oxytocin and CORT increased following the FST regardless of treatment condition (p≤ 0.05). Changes in stress-responsiveness, both behaviourally and hormonally may underlie some deficits in maternal behaviour, thus a clearer understanding of CC’s effect on the stress response system may potentially lead to treatment interventions which could be relevant to clinical populations. Additionally, these results indicate that CC treatment can have long-lasting effects on peripheral oxytocin regulation in rats, similar to changes observed in persistent social behaviour and stress-response deficits in clinical populations.

BackgroundAutism spectrum disorder (ASD) is a heritable, heterogeneous neurodevelopmental disorder that is four times more likely to affect males than females. Despite this overt sex bias, it is unclear how genetic mutations associated with ASD alter cortical circuitry to produce the behavioral phenotypes by which ASD is diagnosed. Contactin-associated protein-like 2 (CNTNAP2) is an ASD-associated gene, and while Cntnap2 knockout (KO) mice recapitulate many of the features of ASD, the effect on cortical circuitry is poorly understood. Moreover, although heterozygous (Het) mice are the more relevant genotype for ASD-linked CNTNAP2 mutations in humans, to our knowledge, no effects in Het mice have been previously reported.MethodsIntrinsic signal optical imaging was used to measure functional visual responses in primary and higher visual cortical areas in male and female Cntnap2 KO, Het, and wild-type (WT) mice. Main effect of genotype was assessed with one-way ANOVA. Visual responses were also measured in P17–18 and P30–32 KO and WT mice. Main effects of age and genotype were assessed using two-way ANOVA.ResultsVisually evoked activity in dorsal stream associated higher visual areas in both KO and Het adult males was decreased relative to WT adult males. This decrease was not observed in adult females. Additionally, no significant difference was observed between WT and KO males at P17–18 with differences beginning to emerge at P30–32.ConclusionsThe functional responses of cortical circuitry in male mice are more strongly affected by Cntnap2 mutations than females, an effect present even in Hets. The observed differences in males emerge with development beginning at P30–32. These results reveal genotype- and sex-dependent effects of altered Cntnap2 expression and can shed light on the sex-dependent incidence of ASD.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-016-9182-5) contains supplementary material, which is available to authorized users.

Background Sensory processing deficits are common in individuals with neurodevelopmental disorders. One hypothesis is that deficits may be more detectable in downstream, “higher” sensory areas. A mouse model of Angelman syndrome (AS), which lacks expression of the maternally inherited Ube3a allele, has deficits in synaptic function and experience-dependent plasticity in the primary visual cortex. Thus, we hypothesized that AS model mice have deficits in visually driven neuronal responsiveness in downstream higher visual areas (HVAs). Methods Here, we used intrinsic signal optical imaging and two-photon calcium imaging to map visually evoked neuronal activity in the primary visual cortex and HVAs in response to an array of stimuli. Results We found a highly specific deficit in HVAs. Drifting gratings that changed speed caused a strong response in HVAs in wildtype mice, but this was not observed in littermate AS model mice. Further investigation with two-photon calcium imaging revealed the effect to be largely driven by aberrant responses of inhibitory interneurons, suggesting a cellular basis for higher level, stimulus-selective cortical dysfunction in AS. Conclusion Assaying downstream, or “higher” circuitry may provide a more sensitive measure for circuit dysfunction in mouse models of neurodevelopmental disorders. Trial registration Not applicable.