Altering the trajectory of early postnatal cortical development can lead to structural and behavioural features of autism

<p>Abstract</p> <p>Background</p> <p>Autism is a behaviourally defined neurodevelopmental disorder with unknown etiology. Recent studies in autistic children consistently point to neuropathological and functional abnormalities in the temporal association cortex (TeA) and its associated structures. It has been proposed that the trajectory of postnatal development in these regions may undergo accelerated maturational alterations that predominantly affect sensory recognition and social interaction. Indeed, the temporal association regions that are important for sensory recognition and social interaction are one of the last regions to mature suggesting a potential vulnerability to early maturation. However, direct evaluation of the emerging hypothesis that an altered time course of early postnatal development can lead to an ASD phenotype remains lacking.</p> <p>Results</p> <p>We used electrophysiological, histological, and behavioural techniques to investigate if the known neuronal maturational promoter valproate, similar to that in culture systems, can influence the normal developmental trajectory of TeA <it>in vivo</it>. Brain sections obtained from postnatal rat pups treated with VPA <it>in vivo </it>revealed that almost 40% of cortical cells in TeA prematurely exhibited adult-like intrinsic electrophysiological properties and that this was often associated with gross cortical hypertrophy and a reduced predisposition for social play behaviour.</p> <p>Conclusions</p> <p>The co-manifestation of these functional, structural and behavioural features suggests that alteration of the developmental time course in certain high-order cortical networks may play an important role in the neurophysiological basis of autism.</p

Sensory input from the osphradium modulates the response to memory-enhancing stressors in Lymnaea stagnalis

SUMMARY In the freshwater environment species often rely on chemosensory information to modulate behavior. The pond snail, Lymnaea stagnalis, is a model species used to characterize the causal mechanisms of long-term memory (LTM) formation. Chemical stressors including crayfish kairomones and KCl enhance LTM formation (≥24 h) in Lymnaea; however, how these stressors are sensed and the mechanism by which they affect the electrophysiological properties of neurons necessary for memory formation are poorly understood. Here, we assessed whether the osphradium, a primary chemosensory organ in Lymnaea, modulates LTM enhancement. To test this we severed the osphradial nerve proximal to the osphradium, using sham-operated animals as controls, and assessed the behavioral and electrophysiological response to crayfish kairomones and KCl. We operantly conditioned aerial respiratory behavior in intact, sham and osphradially cut animals, and tested for enhanced memory formation after exposure to the chemical stressors. Sham-operated animals displayed the same memory enhancement as intact animals but snails with a severed osphradial nerve did not show LTM enhancement. Extracellular recordings made from the osphradial nerve demonstrate that these stressors evoked afferent sensory activity. Intracellular recordings from right pedal dorsal 1 (RPeD1), a neuron necessary for LTM formation, demonstrate that its electrophysiological activity is altered by input from the osphradium following exposure to crayfish kairomones or KCl in sham and intact animals but no response is seen in RPeD1 in osphradially cut animals. Therefore, sensory input from the osphradium is necessary for LTM enhancement following exposure to these chemical stressors.</jats:p

Supplementary_File_2 - Movement Disorders Associated With Antipsychotic Medication in People With Schizophrenia: An Overview of Cochrane Reviews and Meta-Analysis

<p>Supplementary_File_2 for Movement Disorders Associated With Antipsychotic Medication in People With Schizophrenia: An Overview of Cochrane Reviews and Meta-Analysis by Davide Martino, Vikram Karnik, Sydney Osland, Thomas R. E. Barnes, and Tamara M. Pringsheim in The Canadian Journal of Psychiatry</p

Supplementary_File_1 - Movement Disorders Associated With Antipsychotic Medication in People With Schizophrenia: An Overview of Cochrane Reviews and Meta-Analysis

<p>Supplementary_File_1 for Movement Disorders Associated With Antipsychotic Medication in People With Schizophrenia: An Overview of Cochrane Reviews and Meta-Analysis by Davide Martino, Vikram Karnik, Sydney Osland, Thomas R. E. Barnes, and Tamara M. Pringsheim in The Canadian Journal of Psychiatry</p

Transient receptor potential ankyrin 1 receptor activation in vitro and in vivo by pro-tussive agents: GRC 17536 as a promising anti-tussive therapeutic.

Cough is a protective reflex action that helps clear the respiratory tract which is continuously exposed to airborne environmental irritants. However, chronic cough presents itself as a disease in its own right and despite its global occurrence; the molecular mechanisms responsible for cough are not completely understood. Transient receptor potential ankyrin1 (TRPA1) is robustly expressed in the neuronal as well as non-neuronal cells of the respiratory tract and is a sensor of a wide range of environmental irritants. It is fast getting acceptance as a key biological sensor of a variety of pro-tussive agents often implicated in miscellaneous chronic cough conditions. In the present study, we demonstrate in vitro direct functional activation of TRPA1 receptor by citric acid which is routinely used to evoke cough in preclinical and clinical studies. We also show for the first time that a potent and selective TRPA1 antagonist GRC 17536 inhibits citric acid induced cellular Ca(+2) influx in TRPA1 expressing cells and the citric acid induced cough response in guinea pigs. Hence our data provides a mechanistic link between TRPA1 receptor activation in vitro and cough response induced in vivo by citric acid. Furthermore, we also show evidence for TRPA1 activation in vitro by the TLR4, TLR7 and TLR8 ligands which are implicated in bacterial/respiratory virus pathogenesis often resulting in chronic cough. In conclusion, this study highlights the potential utility of TRPA1 antagonist such as GRC 17536 in the treatment of miscellaneous chronic cough conditions arising due to diverse causes but commonly driven via TRPA1