Stimulation Of Vibrissae Research Articles

Remapping of the somatosensory cortex after a photothrombotic stroke: dynamics of the compensatory reorganization

Although stroke can affect cerebral structure and function, the brain has a potential for plasticity thanks to which some degree of function can be restored. The pathways of such recovery are of great interest, since the dynamics of rewiring of the injured brain may become the basis for designing appropriate strategies of rehabilitation. We investigated the spontaneous plasticity of cortical somatosensory representations following a focal unilateral stroke in the barrel cortex of rats. Ischemic lesions were produced with the photothrombotic technique in the cortical representation of vibrissae. Functional activation of the brain in response to the stimulation of vibrissae with destroyed cortical representation was monitored through the 2 months post-stroke survival period with [14C] 2-deoxyglucose (2DG) autoradiographic brain mapping (1, 7, 28, 56 days after the stroke). 2DG uptake was measured on autoradiograms of tangential sections in several regions of somatosensory cortex and in motor, auditory and prefrontal cortex. Behavioral deficit was assessed by the gap-crossing test 3, 28, 56 days after the stroke. Changes in the activation pattern of the intact hemisphere and non-vibrissal somatosensory representations of the lesioned hemisphere evolved during the observation period. Full recovery of the behavioral function was reached 2 months after the stroke and at the same time, new foci of activation were observed in the lesioned hemisphere. At that time, hyperactivation of the somatosensory areas in the intact hemisphere subsided. The new activation foci located in representations of anterior vibrissae, front paw and hind paw were specific for the vibrissae stimulation and were most probably a new functional representation of the vibrissae. We demonstrated spatial and temporal remodeling of the brain induced by cortical stroke, leading to vicariation of function.

Associative pairing involving monocular stimulation selectively mobilizes a subclass of GABAergic interneurons in the mouse visual cortex

Levels of gamma-aminobutyric acid (GABA) and its synthesizing enzyme in cerebral cortex are regulated by sensory experience. Previously we found that associative pairing of vibrissae stimulation and tail shock results in upregulation of GABAergic markers in the mouse barrel cortex. In order to ascertain whether GABAergic upregulation also accompanies associative pairing in other sensory modalities, we examined the mouse visual cortex after analogous training with visual stimulus. During pairing, visual stimulus (CS) was coupled with a tail shock (UCS). We examined the density of cells expressing glutamic acid decarboxylase (GAD) and parvalbumin (PV) in monocular and binocular segments of the primary visual cortex (V1). The auditory cortex was used as a control. After monocular training, the density of cells expressing GAD rose significantly in the monocular segment of V1 contralateral to the stimulated eye, compared with the opposite hemisphere. This effect was due to the association of CS and UCS, as no changes were found after visual stimulation alone or in the auditory cortex. No changes were noted in the density of PV(+) neurons, so the effect was attributed to GAD(+)/PV(-) neurons. Mobilization of a specific subclass of GABAergic cells, observed after associative pairing in the somatosensory and visual cortices, may reflect the necessity to restrict the activity of circuits involved in sensory association.

Mechanical resonance enhances the sensitivity of the vibrissa sensory system to near-threshold stimuli

The representation of high-frequency sensory information is a crucial problem faced by the nervous system. Rodent facial vibrissae constitute a high-resolution sensory system, capable of discriminating and detecting subtle changes in tactual input. During active sensing, the mechanical properties of vibrissae may play a key role in filtering sensory information and translating it into neural activity. Previous studies have shown that rat vibrissae resonate, conferring frequency specificity to trigeminal ganglion (NV) and primary somatosensory cortex (SI) neurons during suprathreshold sensory stimulation. In addition to frequency specificity, a further potential impact of vibrissa resonance is enhancement of sensitivity to near-threshold stimuli through signal amplification. To examine the effect of resonance on peri-threshold inputs (≤ 80 μm at the vibrissa tip), we recorded NV and SI neurons during stimulation at multiple amplitudes and frequencies, and generated minimal amplitude tuning curves. Several novel findings emerged from this study. First, vibrissa resonance significantly lowered the threshold for evoked neural activity, in many cases by an order of magnitude compared to stimuli presented at off-resonance frequencies. When stimulated at the fundamental resonance frequency, motions as small as 8 μm at the vibrissa tip, corresponding to angular deflections of less than 0.2°, drove neural firing in the periphery and cortex. Second, a closer match between vibrissal and neural frequency tuning was found for lower amplitude motions. Third, simultaneous paired recordings demonstrated that the minimal amplitude of resonant vibrissa stimulation required to evoke responses in SI increased significantly for recordings outside the primary vibrissa barrel column, providing additional evidence for somatotopically localized frequency columns. These data demonstrate that resonant amplification can increase the sensitivity of the vibrissa sensory system to an ecologically relevant range of low-amplitude, high-frequency stimuli.

A mouse model for studying large-scale neuronal networks using EEG mapping techniques

Human functional imaging studies are increasingly focusing on the identification of large-scale neuronal networks, their temporal properties, their development, and their plasticity and recovery after brain lesions. A method targeting large-scale networks in rodents would open the possibility to investigate their neuronal and molecular basis in detail. We here present a method to study such networks in mice with minimal invasiveness, based on the simultaneous recording of epicranial EEG from 32 electrodes regularly distributed over the head surface. Spatiotemporal analysis of the electrical potential maps similar to human EEG imaging studies allows quantifying the dynamics of the global neuronal activation with sub-millisecond resolution. We tested the feasibility, stability and reproducibility of the method by recording the electrical activity evoked by mechanical stimulation of the mystacial vibrissae. We found a series of potential maps with different spatial configurations that suggested the activation of a large-scale network with generators in several somatosensory and motor areas of both hemispheres. The spatiotemporal activation pattern was stable both across mice and in the same mouse across time. We also performed 16-channel intracortical recordings of the local field potential across cortical layers in different brain areas and found tight spatiotemporal concordance with the generators estimated from the epicranial maps. Epicranial EEG mapping thus allows assessing sensory processing by large-scale neuronal networks in living mice with minimal invasiveness, complementing existing approaches to study the neurophysiological mechanisms of interaction within the network in detail and to characterize their developmental, experience-dependent and lesion-induced plasticity in normal and transgenic animals.

Acute Functional Recovery of Cerebral Blood Flow after Forebrain Ischemia in Rat

After complete cerebral ischemia, the postischemic blood flow response to functional activation is severely attenuated for several hours. However, little is known about the spatial and temporal extent of the blood flow response in the acute postischemic period after incomplete cerebral ischemia. To investigate the relative cerebral blood flow (rCBF) response in the somatosensory cortex of rat to controlled vibrissae stimulation after transient incomplete ischemia (15-min bilateral common carotid artery occlusion+hypotension), we employed laser speckle imaging combined with statistical parametric mapping. We found that the ischemic insult had a significant impact on the baseline blood flow (P<0.005) and the activation area in response to functional stimulation was significantly reduced after ischemia (P<0.005). The maximum rCBF response in the activation area determined from the statistical analysis did not change significantly up to 3 h after ischemia (P>0.1). However, the time when rCBF response reached its maximum was significantly delayed (P<0.0001) from 2.4+/-0.2 secs before ischemia to 3.6+/-0.1 secs at 20 mins into reperfusion (P<0.001); the delay was reduced gradually to 2.9+/-0.2 secs after 3 h, which was still significantly greater than that observed before the insult (P=0.04).

Laterodorsal nucleus of the thalamus: A processor of somatosensory inputs.

The laterodorsal (LD) nucleus of the thalamus has been considered a "higher order" nucleus that provides inputs to limbic cortical areas. Although its functions are largely unknown, it is often considered to be involved in spatial learning and memory. Here we provide evidence that LD is part of a hitherto unknown pathway for processing somatosensory information. Juxtacellular and extracellular recordings from LD neurons reveal that they respond to vibrissa stimulation with short latency (median = 7 ms) and large magnitude responses (median = 1.2 spikes/stimulus). Most neurons (62%) had large receptive fields, responding to six and more individual vibrissae. Electrical stimulation of the trigeminal nucleus interpolaris (SpVi) evoked short latency responses (median = 3.8 ms) in vibrissa-responsive LD neurons. Labeling produced by anterograde and retrograde neuroanatomical tracers confirmed that LD neurons receive direct inputs from SpVi. Electrophysiological and neuroanatomical analyses revealed also that LD projects upon the cingulate and retrosplenial cortex, but has only sparse projections to the barrel cortex. These findings suggest that LD is part of a novel processing stream involved in spatial orientation and learning related to somatosensory cues.

Sensory learning‐induced enhancement of inhibitory synaptic transmission in the barrel cortex of the mouse

In adult mice, repetitive pairing of stimulation of mystacial vibrissae with an electrical shock to the tail induces expansion of the cortical representation of stimulated vibrissae accompanied by elevation of the GABAergic markers. Here, we show that this associative learning paradigm results in a selective increase in the frequency of spontaneous inhibitory postsynaptic currents in layer IV excitatory neurons located within the barrel representing stimulated vibrissae, evident 24 h after the end of training. The mean amplitude of spontaneous inhibitory postsynaptic potentials recorded from excitatory neurons was unchanged. Recordings from layer IV excitatory and fast spiking neurons showed that the training induced changes neither in the mean frequency nor it the mean amplitude of spontaneous excitatory postsynaptic currents. On the other hand, the mean amplitude of field potentials evoked by the stimulation of layer VI and recorded in layer IV was significantly reduced. These data indicate that aversive training results in a selective and long-lasting enhancement of GABAergic transmission within the cortical representation of stimulated vibrissae, which may result in a decrease in layer VI-evoked field responses.

Repetitive vibrissae-elicited forelimb placing before and immediately after unilateral 6-hydroxydopamine improves outcome in a model of Parkinson's disease

In rodent models of Parkinson's disease (PD), exercise or complex living environments introduced immediately before or during early stages of degeneration can provide beneficial effects on functional and/or neurochemical outcome. The goal of this study was to determine whether or not exposure to repetitive vibrissae-elicited forelimb placing, a dopamine-dependent sensorimotor movement, improves functional outcome in rats infused unilaterally with 6-OHDA. Prior to unilateral 6-OHDA infusions into the medial forebrain bundle, male Sprague–Dawley rats were randomly divided into groups exposed to one of five placing schedules: (1) two consecutive days pre-6-OHDA (PRE), (2) PRE + day 1 post-6-OHDA, (3) PRE + days 1, 2, 3 post-6-OHDA, (4) HANDLE, and (5) Sham infusion + handle. A session consisted of 180 total trials (90 left forelimb and 90 right forelimb trials) including 60 consecutive trials where vibrissae stimulation evoked ipsilateral forelimb movement and 30 consecutive trials where the ipsilateral forelimb was restrained so that vibrissae evoked contralateral forelimb movement (cross-midline placing). All groups were exposed to forelimb placing sessions on post-infusion days 7 and 14. The ability of vibrissae stimulation to elicit an ipsilateral response of the 6-OHDA affected forelimb was assessed on all days. Animals were sacrificed on post-lesion day 15 and substantia nigra tyrosine hydroxylase immunoreactivity (TH-ir) quantified. Repetitive forelimb placing had a significant effect on behavioral performance for all groups compared to the HANDLE group, but only the PRE + 123 group was not significantly different from SHAM controls. Only the PRE + 123 group showed significant sparing of TH-ir compared to the HANDLE group. These data suggest that extensive repetitive exposure to a sensorimotor task may provide therapeutic effects in an animal model of PD.

Focal stroke in the barrel cortex of rats enhances ipsilateral response to vibrissal input

Brain injury triggers spontaneous plasticity, often resulting in considerable restoration of function. To investigate mechanisms of this compensatory plasticity we followed changes in the brain's pattern of activation evoked by stimulation of vibrissae, after a focal cortical stroke which destroyed the cortical representation of vibrissae, the barrel cortex. The pattern of brain activation was visualized with [14C]-2-doexyglucose (2DG) autoradiography in rats 7 days after photothrombotic stroke. During isotope incorporation, vibrissae contralateral to stroke were stimulated. In control rats this stimulation activates the barrel cortex and the second somatosensory cortex in the contralateral hemisphere. Seven days after stroke in the barrel cortex, significant increases in activation were found in ipsilateral, uninjured hemisphere in the barrel cortex and anterior vibrissae representation, and also in regions not specifically connected to vibrissae stimulation, such as motor and auditory cortex. Shortly after cortical stroke, the intact hemisphere shows higher metabolic activation in several cortical regions, possibly due to abnormal interactions with the injured hemisphere.

Cholinergic Regulation of the Posterior Medial Thalamic Nucleus

We previously showed that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incertothalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that this pathway is modulated by the ascending brain stem cholinergic system, which regulates sleep-wake cycles and states of vigilance. We demonstrate that cholinergic inputs facilitate POm responses to vibrissae stimulation. Activation of the cholinergic system by stimulation of brain stem cholinergic nuclei (laterodorsal tegmental and the pedunculopontine tegmental) or by tail pinch significantly increased the magnitude of POm responses to vibrissae stimulation. Microiontophoresis of the muscarinic receptor agonist carbachol enhanced POm responses to vibrissae stimulation. Application of carbachol to an in vitro slice preparation reduced the frequency but not the amplitude of miniature inhibitory postsynaptic currents, indicating a presynaptic site of action for carbachol. We conclude that the cholinergic system facilitates POm responses by suppressing GABAergic inputs from ZI. We propose the state-dependent gating hypothesis, which asserts that differing behavioral states, regulated by the brain stem cholinergic system, modulate the flow of information through POm.

Characterization and plasticity of the double synapse spines in the barrel cortex of the mouse

The somatosensory barrel cortex of rodents and its afferent pathway from the facial vibrissae is a very useful model for studying neuronal plasticity. Dendritic spines are the most labile elements of synaptic circuitry and the most likely substrate of experience-dependent alterations in neuronal circuits in cerebral cortex. We characterized morphologically and numerically a specific population of spines, i.e. double synapse spines, which have two different inputs &amp;#150; one excitatory and the other inhibitory, in the B2 barrel of mouse somatosensory cortex. We also described changes in morphology of double synapse spines induced by classical conditioning in which stimulation of vibrissae was paired with a tail shock. The analysis was carried out by means of serial EM micrograph reconstruction. We showed that double spines account for about 10% of all analyzed spines. The morphology of a typical double synapse spine is similar to the morphology of single synapse spine and both consist of two parts &amp;#150; a large head and a narrow, long neck. Excitatory synapses are preferentially located on the head of double synapse spines and inhibitory synapses are usually located on the neck of these spines. The length of the double synapse spine neck decreases and the cross-section area of the spine neck increases significantly as a result of sensory conditioning. The correspondence should be addressed to E. Pyza, Email: pyza@zuk.iz.uj.edu.pl

Microstimulation of the somatosensory cortex can substitute for vibrissa stimulation during Pavlovian conditioning

The primary somatosensory cortex (S1) contains a map representation of the body surface. We hypothesized that S1 stimulation can successfully substitute for (or be substituted by) direct stimulation of skin receptors. We prepared rabbits for evoking eyelid conditioned responses (CRs) using a trace "shock-air puff" paradigm. In a first series of experiments, animals received a conditioned stimulus (CS, a train of electrical pulses) in the whisker pad or in the S1 areas for vibrissae or for the hind limb. In the three cases, the CS was followed 250 ms from its end by an air puff presented to the cornea as an unconditioned stimulus (US). Learning curves from the three groups presented similar values, although animals stimulated with a central CS acquired their CRs faster. In a second series of experiments, animals were divided into four groups and were presented either centrally or peripherally with the same CS for six conditioning sessions. Then, the CS was switched from central to peripheral, or vice versa, for 5 additional days. Conditioned animals were not able to discriminate between peripheral (vibrissae) stimuli and stimuli presented to the corresponding S1 (vibrissae) area, but they were able to discriminate between CSs presented to S1 (hind limb) and body (vibrissae) regions. The kinetic properties of evoked CRs were not modified by CS switching. It is proposed that S1 allows the construction of somatosensory percepts of the body surface but does not allow distinguishing the central or peripheral location of the evoking stimuli.

Simplified quantification of small animal [18F]FDG PET studies using a standard arterial input function

Arterial input function (AIF) measurement for quantification of small animal PET studies is technically challenging and limited by the small blood volume of small laboratory animals. The present study investigated the use of a standard arterial input function (SAIF) to simplify the experimental procedure. Twelve [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET studies accompanied by serial arterial blood sampling were acquired in seven male Sprague-Dawley rats under isoflurane anaesthesia without (every rat) and with additional (five rats) vibrissae stimulation. A leave-one-out procedure was employed to validate the use of a SAIF with individual scaling by one (1S) or two (2S) arterial blood samples. Automatic slow bolus infusion of [(18)F]FDG resulted in highly similar AIF in all rats. The average differences of the area under the curve of the measured AIF and the individually scaled SAIF were 0.11+/-4.26% and 0.04+/-2.61% for the 1S (6-min sample) and the 2S (4-min/43-min samples) approach, respectively. The average differences between the cerebral metabolic rates of glucose (CMR(glc)) calculated using the measured AIF and the scaled SAIF were 1.31+/-5.45% and 1.30+/-3.84% for the 1S and the 2S approach, respectively. The use of a SAIF scaled by one or (preferably) two arterial blood samples can serve as a valid substitute for individual AIF measurements to quantify [(18)F]FDG PET studies in rats. The SAIF approach minimises the loss of blood and should be ideally suited for longitudinal quantitative small animal [(18)F]FDG PET studies.

Carbamylated Erythropoietin Reduces Radiosurgically-Induced Brain Injury

Gamma knife radiosurgery is an attractive noninvasive treatment of brain tumors and vascular malformations that minimizes collateral tissue damage. However, exposure of normal tissue to even low-dose radiation triggers a cascade of acute and chronic injury and potentially significant morbidity and mortality. Because many irradiated patients now survive for years, identifying methods to prevent radiotherapy-induced collateral tissue damage is a major focus of current research. Erythropoietin (EPO), a cytokine produced locally by many tissues in response to injury, antagonizes apoptosis, reduces inflammation, and promotes healing. Systemic administration of recombinant EPO, widely used for treatment of anemia, provides robust protection from numerous insults in a variety of tissues, including the brain. Although irradiation injury is likely sensitive to EPO, the hematopoietic activity of EPO is undesirable in this setting, increasing erythrocyte number and predisposing to thrombosis. To avoid these potential adverse effects, we developed carbamylated EPO (CEPO) which does not stimulate the bone marrow. In this study, we show that CEPO (50 microg kg(-1) intraperitoneally) improves functional outcome when administered to adult rats just before, and then once daily for 10 d after, a necrotizing dose of radiation (100 Gy) to the right striatum. Immediately following irradiation, use and reflex movements of the contralateral forelimb to vibrissae stimulation were abnormal but rapidly improved in animals receiving CEPO. Moreover, histological examination revealed that the extent of brain necrosis after 90 days was reduced by approximately 50%. These findings further extend the kinds of injury for which administration of a tissue-protective cytokine provides benefit.

Effects of systemically administered cocaine on sensory responses to peri‐threshold vibrissae stimulation: individual cells, ensemble activity, and animal behaviour

Previous studies have shown that systemic administration of cocaine transiently alters stimulus-evoked responses of ventral posteromedial (VPM) thalamic neurons. Results from these single-unit electrophysiological studies revealed that cocaine was equally likely to augment or attenuate the magnitude of sensory evoked responses following threshold level stimulation of peripheral receptive fields. In an attempt to clarify the impact of cocaine administration on sensory signal processing, we examined the drug's effects on responses of individual neurons and ensembles of VPM thalamic neurons to sensory stimuli, and performance of subjects in a sensory detection behavioural task. Extracellular responses of single (n = 1 cell/rat) or multiple VPM thalamic neurons (n = 10-40 cells/rat) were monitored before and after cumulative doses of cocaine (0.25-2.0 mg/kg i.v.). Neuronal responses were characterized by assessing the response profile to a range of peri-threshold-level deflections of the optimal whisker on the contralateral face. Drug effects on stimulus-response curves, determined from quantitative analysis of spike train data, indicated that whereas cocaine elicits variable effects at the single cell level, the stimulus-evoked response of the recorded population was likely to increase following lower (0.25-1.0 mg/kg i.v.) doses of cocaine. Furthermore, cocaine preferentially enhanced responses to smaller magnitude deflections of vibrissa, altering the response profile from a mode that accurately conveyed stimulus strength to one that increased detection at the expense of discrimination. Finally, a similar pattern emerged in a behavioural paradigm involving rats trained to detect variable amplitude whisker pad stimulation, suggesting a common action of cocaine that may contribute to the drug's addictive properties.

Learning-induced plasticity of cortical representations does not affect GAD65 mRNA expression and immunolabeling of cortical neuropil

Two forms of glutamic acid decarboxylase (GAD) are present in inhibitory neurons of the mammalian brain, a 65-kDa isoform (GAD65) and a 67-kDa isoform (GAD67). We have previously found that GAD67 is upregulated during learning-dependent plasticity of cortical vibrissal representations of adult mice. After sensory conditioning involving pairing stimulation of vibrissae with a tail shock, the increase in mRNA expression and density of GAD67-immunoreactive neurons was observed in barrels representing vibrissae activated during the training. In the present study, using the same experimental model, we examined GAD65 mRNA and protein levels in the barrel cortex. For this purpose, we used in situ hybridization and immunohistochemistry. No changes in the level of GAD65 mRNA expression were detected after the training. The pattern of GAD65 mRNA expression was complementary to that observed for GAD67. Immunocytochemical analysis found no changes in immunolabeling of neuropil of the barrels representing the vibrissae activated during the training. The results show that, in contrast to GAD67, cortical plasticity induced by sensory learning does not affect the expression of GAD65.

Postnatal treatment with NAN-190 but not with 5-HT1A receptor agonists retards growth of the rat brain

We investigated the influence of prolonged administration of the 5-HT1A receptor agonists (8-OH-DPAT or buspirone) or its antagonist, NAN-190 to rat pups on development of their cortical barrel field. Pups were injected daily with the drugs starting from the day of birth till either the 5th postnatal day or the 22–25th postnatal day and were perfused one day later. Square areas of their whisker barrel fields were measured on tangential sections of the cortex stained for cytochrome oxidase. Injections of 8-OH-DPAT or buspirone till the 5th postnatal day did not change any of the investigated parameters, while injections of NAN-190 resulted in 15% reduction of the pups’ body and brain weight and proportional reduction of the square area of their barrel fields. Groups treated till the 22–25th postnatal day showed similar results. Some of these pups were injected with [C14]2-deoxyglucose to investigate the strength of responses of their cortical barrels to stimulation of corresponding vibrissae. The cortical area labeled with 2-deoxyglucose after stimulation of vibrissae of the row C was narrower in the NAN-190 injected rats. This functional deficit was more pronounced than the anatomical one, which resembled the effects of neonatal serotonin depletion (Neuroreport, 1997). Therefore, the results of injecting NAN-190 to the rat pups point to a deficit of trophic developmental influences of serotonin, adding new arguments for the hypothesis of a trophic role of 5-HT1A receptors in the brain development.

Testing forelimb placing “across the midline” reveals distinct, lesion-dependent patterns of recovery in rats

We describe a new test of vibrissae-elicited forelimb placing ability that allows testing of sensorimotor integration across the midline. Rats were given unilateral brain lesions using one of three methods: (1) middle cerebral artery occlusion (MCAo) causing significant damage to the cortex and striatum, (2) aspiration lesions to remove tissue from the sensorimotor cortex, and (3) infusions of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, producing a parkinsonian syndrome. Application of the new test to these animals revealed that with some lesion types, the ability of vibrissae on the unimpaired side of the body to trigger placing in the functionally impaired forelimb recovers before vibrissae on the impaired side can elicit placing. This occurs despite the lack of any apparent vibrissae sensory deficit, since the contralesional vibrissae maintained the ability to trigger placing in the unimpaired forelimb in all lesions studied. Chronically, MCAo-lesioned rats do not place the impaired forelimb upon stimulation of the impaired-side vibrissae, but do place if the vibrissae on the good side are stimulated (i.e., when the placing is triggered “across the midline”). This is in contrast to 6-OHDA-lesioned rats which, consistent with parkinsonian akinesia, cannot place the impaired limb regardless of sensory trigger. Also, differences in the pattern of recovery between MCAo- and aspiration-lesioned rats suggest a possible anatomical substrate for cross-midline placing ability and its recovery. Unlike other tests, cross-midline placing methods can readily distinguish between severe stroke and severe parkinsonism in rats.

Optical imaging of the spatiotemporal dynamics of cerebral blood flow and oxidative metabolism in the rat barrel cortex

Oxidative metabolism and cerebral blood flow (CBF) are two of the most important measures in neuroimaging. However, results from concurrent imaging of the two with high spatial and temporal resolution have never been published. We used flavoprotein autofluorescence (AF) and laser speckle imaging (LSI) in the anaesthetized rat to map oxidative metabolism and CBF in response to single vibrissa stimulation. Autofluorescence responses reflecting oxidative metabolism demonstrated a fast increase with a delay of 0.1 s. The sign-reversed speckle contrast reflecting CBF started to rise with a delay of 0.6 s and reached its maximum 1.4 s after the stimulation offset. The fractional signal changes were 2.0% in AF and 9.7% in LSI. Pixelwise modelling revealed that CBF maps spread over an area up to 2.5-times larger than metabolic maps. The results provide evidence that the increase in cerebral oxidative metabolism in response to sensory stimulation is considerably faster and more localized than the CBF response. This suggests that future developments in functional imaging concentrating on the metabolic response promise an increased spatial resolution.

Frequency-dependent processing in the vibrissa sensory system.

The vibrissa sensory system is a key model for investigating principles of sensory processing. Specific frequency ranges of vibrissa motion, generated by rodent sensory behaviors (e.g., active exploration or resting) and by stimulus features, characterize perception by this system. During active exploration, rats typically sweep their vibrissae at approximately 4-12 Hz against and over tactual surfaces, and during rest or quiescence, their vibrissae are typically still (<1 Hz). When a vibrissa is swept over an object, microgeometric surface features (e.g., grains on sandpaper) likely create higher frequency vibrissa vibrations that are greater than or equal to several hundred Hertz. In this article, I first review thalamic and cortical neural responses to vibrissa stimulation at 1-40 Hz. I then propose that neural dynamics optimize the detection of stimuli in low-frequency contexts (e.g., 1 Hz) and the discrimination of stimuli in the whisking frequency range. In the third section, I describe how the intrinsic biomechanical properties of vibrissae, their ability to resonate when stimulated at specific frequencies, may promote detection and discrimination of high-frequency inputs, including textured surfaces. In the final section, I hypothesize that distinct low- and high-frequency processing modes may exist in the somatosensory cortex (SI), such that neural responses to stimuli at 1-40 Hz do not necessarily predict responses to higher frequency inputs. In total, these studies show that several frequency-specific mechanisms impact information transmission in the vibrissa sensory system and suggest that these properties play a crucial role in perception.