In the superficial dorsal horn (SDH) processing of noxious and innocuous stimuli is critically dependent on the input-output relationship of its component neurones. Such relationships are routinely examined by assessing neuronal responses to somatic current injection or activation of synaptic inputs. A more complete understanding of input-output relationships would be achieved by comparing, in the same neurone, how the two forms of activation contribute to neuronal output. Therefore, we examined how SDH neurones transform depolarizing current injections and synaptic excitation via peripheral cutaneous stimuli (brush and pinch of the hindpaw) into trains of action potentials, in an in vivo preparation of the adult mouse spinal cord. Under whole-cell current clamp recording conditions four action potential discharge patterns were observed during depolarizing current injection: tonic firing neurones (21/93) discharged spikes throughout the step; initial bursting neurones (35/93) discharged several spikes at step onset; single spiking neurones (16/93) discharged one or two spikes at step onset; and delayed firing neurones (21/93) discharged spikes delayed from the step onset. Four characteristic profiles were observed in response to application of noxious (pinch) and innocuous (brush) cutaneous stimuli: nociceptive neurones (20/37) responded maximally to pinch stimulation; light touch neurones (9/37) responded maximally to brush stimulation; subthreshold neurones (4/37) exhibited depolarizing responses without firing action potentials; and hyperpolarizing neurones (4/37) exhibited a sustained pinch-induced hyperpolarization. Comparisons of current-evoked discharge patterns with peripherally evoked responses indicate SDH neurones expressing each of the four discharge patterns could receive, and therefore participate in the processing of information concerning, either noxious or innocuous stimuli. These data suggest that a neurone's response to current injection does not necessarily help identify or predict how the same neurone will respond to physiologically or functionally relevant stimuli.
Organic electronic materials have been considered for a wide-range of technological applications. More recently these organic (semi)conductors (encompassing both conducting and semi-conducting organic electronic materials) have received increasing attention as materials for bioelectronic applications. Biological tissues typically comprise soft, elastic, carbon-based macromolecules and polymers, and communication in these biological systems is usually mediated via mixed electronic and ionic conduction. In contrast to hard inorganic semiconductors, whose primary charge carriers are electrons and holes, organic (semi)conductors uniquely match the mechanical and conduction properties of biotic tissue. Here, we review the biocompatibility of organic electronic materials and their implementation in bioelectronic applications.
The mode of synaptic transmission in the vestibular periphery, between type I hair cells and their associated calyx terminal, has been the subject of much debate. The close and extensive apposition of pre- and post-synaptic elements has led some to suggest potassium (K(+)) accumulates in the intercellular space and even plays a role in synaptic transmission. During patch clamp recordings from isolated and embedded hair cells in a semi-intact preparation of the mouse cristae, we noted marked differences in whole-cell currents. Embedded type I hair cells show a prominent droop during steady-state activation as well as a dramatic collapse in tail currents. Responses to a depolarizing voltage step (-124 to +16 mV) in embedded, but not isolated, hair cells resulted in a >40 mV shift of the K(+) equilibrium potential and a rise in effective K(+) concentration (>50 mM) in the intercellular space. Together these data suggest K(+) accumulation in the intercellular space accounts for the different responses in isolated and embedded type I hair cells. To test this notion, we exposed the preparation to hyperosmotic solutions to enlarge the intercellular space. As predicted, the K(+) accumulation effects were reduced; however, a fit of our data with a classic diffusion model suggested K(+) permeability, rather than the intercellular space, had been altered by the hyperosmotic change. These results support the notion that under depolarizing conditions substantial K(+) accumulation occurs in the space between type I hair cells and calyx. The extent of K(+) accumulation during normal synaptic transmission, however, remains to be determined.
Much of our understanding of the neuronal mechanisms of spatial navigation is derived from chronic recordings in rodents in which headdirection, place, and grid cells have all been described. However, despite the proposed importance of self-reference information to these internal representations of space, their congruence with vestibular signaling remains unclear. Here we have undertaken brain-wide functional mapping using both fMRI and electrophysiological methods to directly determine the spatial extent, strength, and time course of vestibular signaling across the rat forebrain. We find distributed activity throughout thalamic, limbic, and particularly primary sensory cortical areas in addition to known head-direction pathways. We also observe activation of frontal regions, including infralimbic and cingulate cortices, indicating integration of vestibular information throughout functionally diverse cortical regions. These whole-brain activity maps therefore suggest a widespread contribution of vestibular signaling to a self-centered framework for multimodal sensorimotor integration in support of movement planning, execution, spatial navigation, and autonomic responses to gravito-inertial changes.
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