Influence of Cholecystokinin-8 on Compound Nerve Action Potentials from Ventral Gastric Vagus in Rats.

OBJECTIVE: Vagus Nerve Stimulation (VNS) has shown great promise as a potential therapy for a number of conditions, such as epilepsy, depression and for Neurometabolic Therapies, especially for treating obesity. The objective of this study was to characterize the left ventral subdiaphragmatic gastric trunk of vagus nerve (SubDiaGVN) and to analyze the influence of intravenous injection of gut hormone cholecystokinin octapeptide (CCK-8) on compound nerve action potential (CNAP) observed on the same branch, with the aim of understanding the impact of hormones on VNS and incorporating the methods and results into closed loop implant design. METHODS: The cervical region of the left vagus nerve (CerVN) of male Wistar rats was stimulated with electric current and the elicited CNAPs were recorded on the SubDiaGVN under four different conditions: Control (no injection), Saline, CCK1 (100[Formula: see text]pmol/kg) and CCK2 (1000[Formula: see text]pmol/kg) injections. RESULTS: We identified the presence of A[Formula: see text], B, C1, C2, C3 and C4 fibers with their respective velocity ranges. Intravenous administration of CCK in vivo results in selective, statistically significant reduction of CNAP components originating from A and B fibers, but with no discernible effect on the C fibers in [Formula: see text] animals. The affected CNAP components exhibit statistically significant ([Formula: see text] and [Formula: see text]) higher normalized stimulation thresholds. CONCLUSION: This approach of characterizing the vagus nerve can be used in closed loop systems to determine when to initiate VNS and also to tune the stimulation dose, which is patient-specific and changes over time.

An array of individually addressable micro-needles for mapping pH distributions.

This work describes the preparation of an array of individually addressable pH sensitive microneedles which are sensitized by electrodepositing iridium oxide. The impact of the deposition potential, storage conditions and interferents on the sensor characteristics such as slope, offset, intra- and inter-batch reproducibility is investigated. The device may be a useful tool for carrying out direct pH measurements of soft and heterogeneous samples such as tissues and organs. For example, we demonstrated that the microneedle array can be employed for real-time mapping of the cardiac pH distribution during cycles of global ischemia and reperfusion.

Purely Translational Realignment in Grid Cell Firing Patterns Following Nonmetric Context Change.

Grid cells in entorhinal and parahippocampal cortices contribute to a network, centered on the hippocampal place cell system, that constructs a representation of spatial context for use in navigation and memory. In doing so, they use metric cues such as the distance and direction of nearby boundaries to position and orient their firing field arrays (grids). The present study investigated whether they also use purely nonmetric "context" information such as color and odor of the environment. We found that, indeed, purely nonmetric cues--sufficiently salient to cause changes in place cell firing patterns--can regulate grid positioning; they do so independently of orientation, and thus interact with linear but not directional spatial inputs. Grid cells responded homogeneously to context changes. We suggest that the grid and place cell networks receive context information directly and also from each other; the information is used by place cells to compute the final decision of the spatial system about which context the animal is in, and by grid cells to help inform the system about where the animal is within it.

Transformation of adaptation and gain rescaling along the whisker sensory pathway.

Neurons in all sensory systems have a remarkable ability to adapt their sensitivity to the statistical structure of the sensory signals to which they are tuned. In the barrel cortex, firing rate adapts to the variance of a whisker stimulus and neuronal sensitivity (gain) adjusts in inverse proportion to the stimulus standard deviation. To determine how adaptation might be transformed across the ascending lemniscal pathway, we measured the responses of single units in the first and last subcortical stages, the trigeminal ganglion (TRG) and ventral posterior medial thalamic nucleus (VPM), to controlled whisker stimulation in urethane-anesthetized rats. We probed adaptation using a filtered white noise stimulus that switched between low- and high-variance epochs. We found that the firing rate of both TRG and VPM neurons adapted to stimulus variance. By fitting the responses of each unit to a Linear-Nonlinear-Poisson model, we tested whether adaptation changed feature selectivity and/or sensitivity. We found that, whereas feature selectivity was unaffected by stimulus variance, units often exhibited a marked change in sensitivity. The extent of these sensitivity changes increased systematically along the pathway from TRG to barrel cortex. However, there was marked variability across units, especially in VPM. In sum, in the whisker system, the adaptation properties of subcortical neurons are surprisingly diverse. The significance of this diversity may be that it contributes to a rich population representation of whisker dynamics.

Sensory input drives multiple intracellular information streams in somatosensory cortex.

Stable perception arises from the interaction between sensory inputs and internal activity fluctuations in cortex. Here we analyzed how different types of activity contribute to cortical sensory processing at the cellular scale. We performed whole-cell recordings in the barrel cortex of anesthetized rats while applying ongoing whisker stimulation and measured the information conveyed about the time-varying stimulus by different types of input (membrane potential) and output (spiking) signals. We found that substantial, comparable amounts of incoming information are carried by two types of membrane potential signal: slow, large (up-down state) fluctuations, and faster (>20 Hz), smaller-amplitude synaptic activity. Both types of activity fluctuation are therefore significantly driven by the stimulus on an ongoing basis. Each stream conveys essentially independent information. Output (spiking) information is contained in spike timing not just relative to the stimulus but also relative to membrane potential fluctuations. Information transfer is favored in up states relative to down states. Thus, slow, ongoing activity fluctuations and finer-scale synaptic activity generate multiple channels for incoming and outgoing information within barrel cortex neurons during ongoing stimulation.

Diverse and temporally precise kinetic feature selectivity in the VPm thalamic nucleus.

The thalamo-cortical pathway is the crucial sensory gateway into the cerebral cortex. We aimed to determine the nature of the tactile information encoded by neurons in the whisker somatosensory relay nucleus (VPm). We wanted to distinguish whether VPm neurons encode similar stimulus features, acting as a single information channel, or encode diverse features. We recorded responses to whisker deflections that thoroughly explored the space of temporal stimulus variables and identified features to which neurons were selective by reverse correlation. The timescale of the features was typically 1-2 ms, at the limit imposed by our experimental conditions, indicating highly acute feature selectivity. Sensitivity to stimulus kinetics was strikingly diverse. Some neurons (25%) only encoded velocity; others were sensitive to position, acceleration, or more complex features. A minority (19%) encoded two or more features. These results indicate that VPm contains a distributed representation of whisker motion, based on high-resolution kinetic features.

Role of precise spike timing in coding of dynamic vibrissa stimuli in somatosensory thalamus.

Rats discriminate texture by whisking their vibrissae across the surfaces of objects. This process induces corresponding vibrissa vibrations, which must be accurately represented by neurons in the somatosensory pathway. In this study, we investigated the neural code for vibrissa motion in the ventroposterior medial (VPm) nucleus of the thalamus by single-unit recording. We found that neurons conveyed a great deal of information (up to 77.9 bits/s) about vibrissa dynamics. The key was precise spike timing, which typically varied by less than a millisecond from trial to trial. The neural code was sparse, the average spike being remarkably informative (5.8 bits/spike). This implies that as few as four VPm spikes, coding independent information, might reliably differentiate between 10(6) textures. To probe the mechanism of information transmission, we compared the role of time-varying firing rate to that of temporally correlated spike patterns in two ways: 93.9% of the information encoded by a neuron could be accounted for by a hypothetical neuron with the same time-dependent firing rate but no correlations between spikes; moreover, > or =93.4% of the information in the spike trains could be decoded even if temporal correlations were ignored. Taken together, these results suggest that the essence of the VPm code for vibrissa motion is firing rate modulation on a submillisecond timescale. The significance of such a code may be that it enables a small number of neurons, firing only few spikes, to convey distinctions between very many different textures to the barrel cortex.

Cholinergic modulation of sensory interference in rat primary somatosensory cortical neurons.

Sensory interaction was studied using extracellular recordings from 275 neurons in the primary somatosensory (SI) cortex of pentobarbital-anesthetized rats. Tactile stimulation was applied to the receptive field using a 1 mm diameter probe that indented the skin for 20 ms, at 0.5 Hz, (test stimulus). Tactile test responses of SI neurons decreased during simultaneous application of a gentle tickling (distracter stimuli) continuously for 60 s on a separate receptive field located in the same or the contralateral hindlimb (ipsi- or contralateral distraction). This decrease in neural response produced by distracter stimuli was interpreted as "sensory interference". Sensory interference was observed in 66% and 61% of recorded SI neurons when ipsi- or contralateral distracters were applied, respectively and was blocked by a novel stimulus obtained by increasing the stimulation frequency of the test tactile stimuli from 0.5 to 2 Hz. The number of neurons showing sensory interference in response to a contralateral distracter was not modified after corpus callosum transection, suggesting that interhemispheric connections are not crucial for sensory interference. In contrast, the number of neurons showing sensory interference decreased in animals with 192 IgG-saporin basal forebrain lesions that decreased the number of cortical cholinergic fibers. This finding indicates that cholinergic afferents from the basal forebrain are fundamental to sensory interference and suggests that the associative cortices - basal forebrain - sensory cortices network may be implicated in sensory interference.

Sensory-interference in rat primary somatosensory cortical neurons.

To study sensory interaction in the primary somatosensory cortex (SI), we registered 221 neurons in the SI of pentobarbital-anaesthetized Wistar rats. Tactile stimulation was applied in the receptive field of the SI neuron with an electronically controlled probe (20 ms duration). Tactile stimulation elicited 2.33 +/- 0.13 spikes per stimulus in SI neurons. Simultaneous application of paintbrush tickles of the contralateral limb usually decreased tactile responses (1.59 +/- 0.11 spikes per stimulus). This effect was considered a 'sensory-interference'. Light flashes applied at random did not modify tactile response. Applying atropine (1 mm), a muscarinic receptor antagonist, and bicuculline (1 mm), a GABAA receptor antagonist, to the SI cortex blocked the sensory-interference effect, while application of mecamylamine (10 mm), a nicotinic cholinergic receptor antagonist, did not affect sensory-interference. Results reveal sensory interactions in SI cortex that control tactile responses, and suggest the participation of the basal forebrain in the sensory-interference effect.