Neuroscience
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Deafness is a genetically complex disorder with many contributing genes still unknown. Here we describe the expression of Pitpnm1 in the inner ear. It is expressed in the inner hair cells of the organ of Corti from late embryonic stages until adulthood, and transiently in the outer hair cells during early postnatal stages. Despite this specific expression, Pitpnm1 null mice showed no hearing defects, possibly due to redundancy with the paralogous genes Pitpnm2 and Pitpnm3.
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Individuals are exposed to stressful events in their daily life. The effects of stress on brain function ranges from highly adaptive to increasing the risk to develop psychopathology. For example, stressful experiences are remembered well which can be seen as a highly appropriate behavioral adaptation. ⋯ An important question that remains to be addressed is how stress regulates brain function and what determines the threshold between adaptive and maladaptive responses. Excitatory synapses play a crucial role in synaptic transmission, synaptic plasticity and behavioral adaptation. In this review we discuss how brief and prolonged exposure to stress, in adulthood and early life, regulate the function of these synapses, and how these effects may contribute to behavioral adaptation and psychopathology.
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Review
Prenatal ontogeny as a susceptibility period for cortical GABA neuron disturbances in schizophrenia.
Cognitive deficits in schizophrenia have been linked to disturbances in GABA neurons in the prefrontal cortex (PFC). Furthermore, cognitive deficits in schizophrenia appear well before the onset of psychosis and have been reported to be present during early childhood and even during the first year of life. Taken together, these data raise the following question: Does the disease process that produces abnormalities in prefrontal GABA neurons in schizophrenia begin prenatally and disrupt the ontogeny of cortical GABA neurons? Here, we address this question through a consideration of evidence that genetic and/or environmental insults that occur during gestation initiate a pathogenetic process that alters cortical GABA neuron ontogeny and produces the pattern of GABA neuron abnormalities, and consequently cognitive difficulties, seen in schizophrenia. ⋯ Third, we discuss recent studies demonstrating altered expression of these ontogenetic factors in the PFC in schizophrenia. Fourth, we discuss the potential role of disturbances in the maternal-fetal environment such as maternal immune activation in the development of GABA neuron dysfunction. Finally, we propose critical questions that need to be answered in future research to further investigate the role of altered GABA neuron ontogeny in the pathogenesis of schizophrenia.
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A number of psychiatric illnesses have been associated with prenatal disturbance of brain development, including autism, attention deficit hyperactivity disorder, and schizophrenia. Individuals afflicted with these disorders exhibit both repetitive motor and cognitive behavior. The potential role that environmental insult to the developing brain may play in generating these aberrant behaviors is unclear. ⋯ Perseverative errors and non-perseverative errors were recorded in early stages of the testing, at the 0 delay interval. While performing DA, FIMs made more errors of perseveration than CONs yet the number of total errors committed did not differ between groups. The presence of motor stereotypies and cognitive perseveration in fetally irradiated non-human primates suggests that environmental insult to the embryonic brain may contribute to repetitive motor and cognitive behaviors in neuropsychiatric diseases.
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In adult animals, the cerebellum is richly innervated by serotonin: serotonergic fibres are the third main afferent fibres into the cerebellum. However, the physiology of the serotonergic system and its functional significance are not fully known during development in the cerebellum. In this review we will focus on the serotonergic regulation of the cerebellum during postnatal development. ⋯ Thus, we propose that serotonin controls cerebellar development in three phases: (1) stimulation of dendritic growth and formation of synapses, (2) hard-wiring of neuronal connections with limits to dendritic growth but ensuring synaptic plasticity, and (3) stabilization of synapses. Taken together, serotonin receptors expressed by different cells in the cerebellum have a specialized role during postnatal development, but with some similar main effects. Distinct spatial and temporal expression of these receptors gives serotonin a powerful and specific role in cerebellar development.