Membrane Potential Correlates of Network Decorrelation and Improved SNR by Cholinergic Activation in the Somatosensory Cortex.

The nucleus basalis (NB) projects cholinergic axons to the cortex, where they play a major role in arousal, attention, and learning. Cholinergic inputs shift cortical dynamics from synchronous to asynchronous and improve the signal-to-noise ratio (SNR) of sensory responses. However, the underlying mechanisms of these changes remain unclear. Using simultaneous extracellular and whole-cell patch recordings in layer 4 of the mouse barrel cortex, we show that electrical or optogenetic activation of the cholinergic system has a differential effect on ongoing and sensory evoked activities. Cholinergic activation profoundly reduced the large spontaneous fluctuations in membrane potential and decorrelated ongoing activity. However, NB stimulation had no effect on the response to whisker stimulation or on signal correlations. These effects of cholinergic activation provide a unified explanation for the increased SNR of sensory response and for the reduction in noise correlations and explain the shift into the desynchronized cortical state, which are the hallmarks of arousal and attention.SIGNIFICANCE STATEMENT Attention increases the signal-to-noise ratio (SNR) of cortical sensory response, which may reflect either reduction in background firing rate or increased sensory response. Extracellular recordings showed that attention also reduces the correlation in network activity. These effects are partially mediated by cholinergic axons from the nucleus basalis projecting to the entire cortex. To reveal the cellular and synaptic correlates of these cholinergic effects, we performed simultaneous intracellular and LFP recordings in the somatosensory cortex. Global or local cholinergic activation increased the SNR of sensory response mainly by reducing the rate and amplitude of background synaptic activity and also reduced network correlations. Therefore, coding of sensory information is enhanced by the cholinergic system mainly due to a reduction in spontaneous activity.

The effectiveness of an outdoor adventure programme for young children with autism spectrum disorder: a controlled study.

AIM: Outdoor adventure programmes aim to improve interpersonal relationships using adventurous activities. The current study examined the effectiveness of an outdoor adventure programme in children with autism spectrum disorders (ASD). METHOD: The study included 51 participants (40 males, 11 females; age 3y 4mo-7y 4mo) enrolled in ASD special education kindergartens. Only the intervention group (n=30) participated in the outdoor adventure programme for 13 weeks, completing challenging physical activities that required cooperation and communication with peers and instructors. The control group (n=21) was not significantly different from the research group in age, sex, cognitive, and adaptive behaviour measures. RESULTS: Outcomes after the intervention revealed significant improvement in social-communication and different directions in the two groups in the social cognition, social motivation, and autistic mannerisms subdomains of the Social Responsiveness Scale. While the group that received an outdoor adventure programme showed a tendency toward a reduction in severity, the control group showed the opposite (p<0.010). INTERPRETATION: The outdoor adventure programme required problem-solving skills and forced the child to communicate in exciting situations. This study suggests that an outdoor adventure programme may be an effective intervention in addition to traditional treatments in young children with ASD. Future studies should examine the outcome of outdoor adventure programmes delivered for longer periods of time and maintenance of the achievements over time.

Structure-function correlations of rat trigeminal primary neurons: Emphasis on club-like endings, a vibrissal mechanoreceptor.

This study focuses on the structure and function of the primary sensory neurons that innervate vibrissal follicles in the rat. Both the peripheral and central terminations, as well as their firing properties were identified using intracellular labelling and recording in trigeminal ganglia in vivo. Fifty-one labelled neurons terminating peripherally, as club-like, Merkel, lanceolate, reticular or spiny endings were identified by their morphology. All neurons responded robustly to air puff stimulation applied to the vibrissal skin. Neurons with club-like endings responded with the highest firing rates; their peripheral processes rarely branched between the cell body and their terminal tips. The central branches of these neurons displayed abundant collaterals terminating within all trigeminal nuclei. Analyses of three-dimensional reconstructions reveal a palisade arrangement of club-like endings bound to the ringwulst by collagen fibers. Our morphological findings suggest that neurons with club-like endings sense mechanical aspects related to the movement of the ringwulst and convey this information to all trigeminal nuclei in the brainstem.

Bmp5/7 in concert with the mid-hindbrain organizer control development of noradrenergic locus coeruleus neurons.

The locus coeruleus (LC) which is the major noradrenergic nucleus in the brain develops under the influence of Bmps secreted by the roof plate and Fgf8 emitted from the mid-hindbrain organizer. We studied the development of the LC in different Bmp mouse mutants and report the absence of this nucleus in Bmp5(-/-);Bmp7(-/-) double knockouts. Notably, genes marking organizers and neuronal populations adjacent to the LC precursor field are unperturbed in Bmp5(-/-);Bmp7(-/-) animals. In addition, we found that in En1(+/Otx2) mutants in which the caudal Otx2 expression domain and thereby the mid-hindbrain organizer are shifted caudally, LC neurons are concomitantly reduced along with Bmp5/7. Complementing these results, Otx1(-/-);Otx2(+/-) mutants, in which the mid-hinbrain organizer is shifted rostrally, show a rostrally extended Bmp5 expression area and an increase in LC neurons. Taken together, our data indicate that LC development requires either Bmp5 or Bmp7, and one is able to compensate for the loss of the other. In addition, we conclude that the position of the mid-hindbrain organizer determines the size of the LC and propose that Bmp5/7 play an important role in mediating this organizer function.