The Journal of neuroscience : the official journal of the Society for Neuroscience
-
Despite their routine use during surgical procedures, no consensus has yet been reached on the precise mechanisms by which hypnotic anesthetic agents produce their effects. Molecular, animal and human studies have suggested disruption of thalamocortical communication as a key component of anesthetic action at the brain systems level. Here, we used the anesthetic agent, propofol, to modulate consciousness and to evaluate differences in the interactions of remote neural networks during altered consciousness. ⋯ We considered the data as a graph, or complex network of nodes and links, and used eigenvector centrality (EC) to characterize brain network properties. The EC mapping of fMRI data in healthy humans under propofol mild sedation demonstrated a decrease of centrality of the thalamus versus an increase of centrality within the pons of the brainstem, highlighting the important role of these two structures in regulating consciousness. Specifically, the decrease of thalamus centrality results from its disconnection from a widespread set of cortical and subcortical regions, while the increase of brainstem centrality may be a consequence of its increased influence, in the mildly sedated state, over a few highly central cortical regions key to the default mode network such as the posterior and anterior cingulate cortices.
-
Spinal cord injury (SCI) results not only in motor deficits, but produces, in many patients, excruciating chronic pain (SCI pain). We have previously shown, in a rodent model, that SCI causes suppression of activity in the GABAergic nucleus, the zona incerta (ZI), and concomitant increased activity in one of its main targets, the posterior nucleus of the thalamus (PO); the increased PO activity is correlated with the maintenance and expression of hyperalgesia after SCI. Here, we test the hypothesis that SCI causes a similar pathological increase in other thalamic nuclei regulated by the ZI, specifically the mediodorsal thalamus (MD), which is involved in the emotional-affective aspects of pain. ⋯ Consistent with our hypothesis, MD neurons from rats with SCI show significant increases in spontaneous firing rates and in the magnitude and duration of responses to noxious stimuli. In a subset of anesthetized animals, similar changes in activity of MD neurons were produced by pharmacologically inactivating ZI in naive rats, suggesting that the changes in the MD after SCI are related to suppressed inhibition from the ZI. These data support our hypothesis that SCI pain results, at least in part, from a loss of inhibition to thalamic nuclei associated with both the sensory-discriminative and emotional-affective components of pain.
-
Sox2 is required for proper neuronal formation in the CNS, but the molecular mechanisms involved are not well characterized. Here, we addressed the role of Sox2 in neurogenesis of the developing chicken inner ear. Overexpressing Sox2 from a constitutive (β-actin) promoter induces the expression of the proneural gene, Neurogenin1 (Ngn1); however, the expression of a downstream target of Ngn1, Neurod1, is unchanged. ⋯ These results suggest that high levels of Sox2 inhibit progression of neurogenesis in the developing inner ear. Furthermore, we provide evidence that Ngn1 and Neurod1 inhibit Sox2 transcription through a phylogenetically conserved Sox2 enhancer to mediate neurogenesis. We propose that Sox2 confers neural competency by promoting Ngn1 expression, and that negative feedback inhibition of Sox2 by Ngn1 is an essential step in the progression from neural precursor to nascent neuron.
-
During an early epoch of development, the brain is highly adaptive to the stimulus environment. Exposing young animals to a particular tone, for example, leads to an enlarged representation of that tone in primary auditory cortex. While the neural effects of simple tonal environments are well characterized, the principles that guide plasticity in more complex acoustic environments remain unclear. ⋯ To address these questions, we reared juvenile rats in complex multitone environments that differed in terms of the higher-order conditional probabilities between sounds. We found that the development of primary cortical acoustic representations, as well as frequency discrimination ability in adult animals, were shaped by the higher-order stimulus statistics of the early acoustic environment. Our results suggest that early experience-dependent cortical reorganization may mediate perceptual changes through statistical learning of the sensory input.
-
Synaptic transmission depends on the matching and alignment of presynaptically released transmitters and postsynaptic neurotransmitter receptors. Neuroligin (NL) and Neurexin (Nrxn) proteins are trans-synaptic adhesion molecules that are important in validation and maturation of specific synapses. ⋯ This specificity is conferred by presynaptic Nrxn isoforms, as NL1 can also induce functional inhibitory synapse connections when the presynaptic interneurons ectopically express an Nrxn isoform that binds to NL1. Our results indicate that trans-synaptic interaction with differentially expressed presynaptic Nrxns underlies the distinct functions of NL1 and NL2, and is sufficient to induce functional inhibitory synapse formation.