Cortex dynamically modulates responses of thalamic relay neurons through prolonged circuit-level disinhibition in rat thalamus in vivo.

Cortex actively modulates the responses of thalamic relay neurons through corticothalamic (CT) projections. Here we investigated the temporal precision of CT modulation on sensory responses of relay neurons in rat ventral posterior medial thalamus (VPM) to direction-specific whisker stimuli. CT feedback levels were either augmented by cortical electrical microstimulation or depressed by cortical application of muscimol, a potent agonist of γ-aminobutyric acid A-type (GABAA) receptors. To evaluate the temporal specificity of CT influence, we compared the early (3-10 ms after stimulus onset) and late (10-100 ms) response components of VPM single units to whisker deflections in preferred or nonpreferred directions before and after altering CT feedback levels under urethane anesthesia. The data showed that cortical feedback most strongly affected the late responses of single VPM units to whisker stimulation. That is, cortical stimulation consistently increased the late responses of VPM units in the corresponding (homologous) barreloids to the stimulus direction preferred by neurons in the cortical locus stimulated. However, cortical stimulation could either increase or decrease the early response, depending on whether or not cortical and thalamic loci were tuned to the same direction. Such bidirectional regulation of the early and late VPM responses is consistent with a mechanism of circuit-level disinhibition in vivo. The results support the theory that CT feedback on thalamic sensory responses is mediated by a time-dependent shift of the excitation-inhibition balance in the thalamo-cortico-thalamic loop, such as would occur during sensory feature integration, plasticity, and learning in the awake state.

In vivo quantitative proteomics of somatosensory cortical synapses shows which protein levels are modulated by sensory deprivation.

Postnatal bilateral whisker trimming was used as a model system to test how synaptic proteomes are altered in barrel cortex by sensory deprivation during synaptogenesis. Using quantitative mass spectrometry, we quantified more than 7,000 synaptic proteins and identified 89 significantly reduced and 161 significantly elevated proteins in sensory-deprived synapses, 22 of which were validated by immunoblotting. More than 95% of quantified proteins, including abundant synaptic proteins such as PSD-95 and gephyrin, exhibited no significant difference under high- and low-activity rearing conditions, suggesting no tissue-wide changes in excitatory or inhibitory synaptic density. In contrast, several proteins that promote mature spine morphology and synaptic strength, such as excitatory glutamate receptors and known accessory factors, were reduced significantly in deprived synapses. Immunohistochemistry revealed that the reduction in SynGAP1, a postsynaptic scaffolding protein, was restricted largely to layer I of barrel cortex in sensory-deprived rats. In addition, protein-degradation machinery such as proteasome subunits, E2 ligases, and E3 ligases, accumulated significantly in deprived synapses, suggesting targeted synaptic protein degradation under sensory deprivation. Importantly, this screen identified synaptic proteins whose levels were affected by sensory deprivation but whose synaptic roles have not yet been characterized in mammalian neurons. These data demonstrate the feasibility of defining synaptic proteomes under different sensory rearing conditions and could be applied to elucidate further molecular mechanisms of sensory development.

Unilateral whisker trimming in newborn rats alters neuronal coincident discharge among mature barrel cortex neurons.

It is known that sensory deprivation, including postnatal whisker trimming, can lead to severe deficits in the firing rate properties of cortical neurons. Recent results indicate that development of synchronous discharge among cortical neurons is also activity influenced, and that correlated discharge is significantly impaired following loss of bilateral sensory input in rats. Here we investigate whether unilateral whisker trimming (unilateral deprivation or UD) after birth interferes in the same way with the development of synchronous discharge in cortex. We measured the coincidence of spikes among pairs of neurons recorded under urethane anesthesia in one whisker barrel field deprived by trimming all contralateral whiskers for 60 days after birth (UD), and in untrimmed controls (CON). In the septal columns around barrels, UD significantly increased the coincident discharge among cortical neurons compared with CON, most notably in layers II/III. In contrast, synchronous discharge was normal between layer IV UD barrel neurons: i.e., not different from CON. Thus, while bilateral whisker deprivation (BD) produced a global deficit in the development of synchrony in layer IV, UD did not block the development of synchrony between neurons in layer IV barrels and increased synchrony within septal circuits. We conclude that changes in synchronous discharge after UD are unexpectedly different from those recorded after BD, and we speculate that this effect may be due to the driven activity from active commissural inputs arising from the contralateral hemisphere that received normal activity levels during postnatal development.

Voltage-sensitive dye imaging reveals shifting spatiotemporal spread of whisker-induced activity in rat barrel cortex.

In rats, navigating through an environment requires continuous information about objects near the head. Sensory information such as object location and surface texture are encoded by spike firing patterns of single neurons within rat barrel cortex. Although there are many studies using single-unit electrophysiology, much less is known regarding the spatiotemporal pattern of activity of populations of neurons in barrel cortex in response to whisker stimulation. To examine cortical response at the population level, we used voltage-sensitive dye (VSD) imaging to examine ensemble spatiotemporal dynamics of barrel cortex in response to stimulation of single or two adjacent whiskers in urethane-anesthetized rats. Single whisker stimulation produced a poststimulus fluorescence response peak within 12-16 ms in the barrel corresponding to the stimulated whisker (principal whisker). This fluorescence subsequently propagated throughout the barrel field, spreading anisotropically preferentially along a barrel row. After paired whisker stimulation, the VSD signal showed sublinear summation (less than the sum of 2 single whisker stimulations), consistent with previous electrophysiological and imaging studies. Surprisingly, we observed a spatial shift in the center of activation occurring over a 10- to 20-ms period with shift magnitudes of 1-2 barrels. This shift occurred predominantly in the posteromedial direction within the barrel field. Our data thus reveal previously unreported spatiotemporal patterns of barrel cortex activation. We suggest that this nontopographical shift is consistent with known functional and anatomic asymmetries in barrel cortex and that it may provide an important insight for understanding barrel field activation during whisking behavior.

Cross-sensory modulation of primary sensory cortex is developmentally regulated by early sensory experience.

The presence of cross-sensory influences on neuronal responses in primary sensory cortex has been observed previously using several different methods. To test this idea in rat S1 barrel cortex, we hypothesized that auditory stimuli combined with whisker stimulation ("cross-sensory" stimuli) may modify response levels to whisker stimulation. Since the brain has been shown to have a remarkable capacity to be modified by early postnatal sensory activity, manipulating postnatal sensory experiences would be predicted to alter the degree of cross-sensory interactions. To test these ideas, we raised rats with or without whisker deprivation and with or without postnatal exposure to repeated auditory clicks. We recorded extracellular responses under urethane anesthesia from barrel cortex neurons in response to principal whisker stimulation alone, to auditory click stimulation alone, or to a cross-sensory stimulus. The responses were compared statistically across different stimulus conditions and across different rearing groups. Barrel neurons did not generate action potentials in response to auditory click stimuli alone in any rearing group. However, in cross-sensory stimulus conditions the response magnitude was facilitated in the 0-15 ms post-whisker-stimulus epoch in all rearing conditions, whereas modulation of response magnitude in a later 15-30 ms post-whisker-stimulus epoch was significantly different in each rearing condition. The most significant cross-sensory effect occurred in rats that were simultaneously whisker deprived and click reared. We conclude that there is a modulatory type of cross-sensory auditory influence on normal S1 barrel cortex, which can be enhanced by early postnatal experiences.

Early bilateral sensory deprivation blocks the development of coincident discharge in rat barrel cortex.

Several theories have proposed a functional role for synchronous neuronal firing in generating the neural code of a sensory perception. Synchronous neural activity develops during a critical postnatal period of cortical maturation, and severely reducing neural activity in a sensory pathway during this period could interfere with the development of coincident discharge among cortical neurons. Loss of such synchrony could provide a fundamental mechanism for the degradation of acuity shown in behavioral studies. We tested the hypothesis that synchronous discharge of barrel cortex neurons would fail to develop after sensory deprivation produced by bilateral whisker trimming from birth to postnatal day 60. By studying the correlated discharge of cortical neuron pairs, we found evidence for strong correlated firing in control animals, and this synchrony was almost absent among pairs of cortical barrel neurons in deprived animals. The degree of synchrony impairment was different in subregions of rat barrel cortex. The model that best fits the data is that cortical neurons receiving direct inputs from the primary sensory (lemniscal) pathway show the greatest decrement in synchrony following sensory deprivation, while neurons with diverse inputs from other areas of thalamus and cortex are relatively less affected in this dimension of cortical function.

Neonatal sensory deprivation and the development of cortical function: unilateral and bilateral sensory deprivation result in different functional outcomes.

The normal development of sensory perception in mammals depends on appropriate sensory experience between birth and maturity. Numerous reports have shown that trimming some or all of the large mystacial vibrissa (whiskers) on one side of the face after birth has a detrimental effect on the maturation of cortical function. The objective of the present study was to understand the differences that occur after unilateral whisker trimming compared with those that occur after bilateral deprivation. Physiological deficits produced by bilateral trimming (BD) of all whiskers for 2 mo after birth were compared with the deficits produced by unilateral trimming (UD) for the same period of time using extracellular recording under urethan anesthesia from single cells in rat barrel cortex. Fast spiking (FSUs) and regular spiking (RSUs) units were separated and their properties compared in four subregions identified by histological reconstructions of the electrode penetrations, namely: layer IV barrel and septum, and layers II/III above a barrel and above a septum. UD upregulated responses in layer IV septa and in layers II/III above septa and perturbed the timing of responses to whisker stimuli. After BD, nearly all responses were decreased, and poststimulus latencies were increased. Circuit changes are proposed as an argument for how inputs arising from the spared whiskers project to the undeprived cortex and, via commissural fibers, could upregulate septal responses after UD. Following BD, more global neural deficits create a signature difference in the outcome of UD and BD in rat barrel cortex.

Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion.

A highly interconnected network of arterioles overlies mammalian cortex to route blood to the cortical mantle. Here we test if this angioarchitecture can ensure that the supply of blood is redistributed after vascular occlusion. We use rodent parietal cortex as a model system and image the flow of red blood cells in individual microvessels. Changes in flow are quantified in response to photothrombotic occlusions to individual pial arterioles as well as to physical occlusions of the middle cerebral artery (MCA), the primary source of blood to this network. We observe that perfusion is rapidly reestablished at the first branch downstream from a photothrombotic occlusion through a reversal in flow in one vessel. More distal downstream arterioles also show reversals in flow. Further, occlusion of the MCA leads to reversals in flow through approximately half of the downstream but distant arterioles. Thus the cortical arteriolar network supports collateral flow that may mitigate the effects of vessel obstruction, as may occur secondary to neurovascular pathology.

Adaptive filtering of vibrissa input in motor cortex of rat.

We studied the transformation of sensory input as it progresses from vibrissa primary sensor (S1) to motor (M1) cortex. Single-unit activity was obtained from alert adult rats that did not to whisk upon application of punctate, rhythmic stimulation of individual vibrissae. The spike response of units in S1 cortex largely reproduced the shape of the stimulus. In contrast, the spiking output of units in M1 cortex were modulated solely as a sinusoid at the repetition rate of the stimulus for frequencies between 5 and 15 Hz; this range corresponds to that of natural whisking. Thus, the S1 to M1 transformation extracts the fundamental frequency from a spectrally rich stimulus. We discuss our results in terms of a band-pass filter with a center frequency that adapts to the change in stimulation rate.

Cortical modulation of spatial and angular tuning maps in the rat thalamus.

The massive feedback projections from cortex to the thalamus modulate sensory information transmission in many ways. We investigated the role of corticothalamic feedback projections on the directional selectivity (angular tuning) of neurons in the rat ventral posterior medial (VPM) nucleus to stimulation of their principal whisker. The angular tuning properties of single VPM neurons were compared before and after epochs of electrical stimulation of layer VI feedback neurons in the ipsilateral cortex under urethane anesthesia. Microstimulation of layer VI in "matched" (homologous) barrel columns sharpens the angular tuning curves of single VPM neurons that are tuned to the same direction as the stimulation site in the cortex. Further, microstimulation rotates the angular preference of VPM neurons initially tuned to a different direction toward the direction that cortical neurons prefer. Stimulation in "mismatched" (nonhomologous) barrel columns suppresses responses without consistent effects on angular tuning. We conclude that the primary sensory cortex exerts a significant influence on both spatial and angular tuning maps in the relay nuclei that project to it. The results suggest that the tuning properties of VPM cells in the behaving animal are continually modified to optimize perception of the most salient incoming messages.

Prenatal exposure to benzo(a)pyrene impairs later-life cortical neuronal function.

Prenatal exposure to environmental contaminants, such as benzo(a)pyrene [B(a)P] has been shown to impair brain development. The overarching hypothesis of our work is that glutamate receptor subunit expression is crucial for cortical evoked responses and that prenatal B(a)P exposure modulates the temporal developmental expression of glutamatergic receptor subunits in the somatosensory cortex. To characterize prenatal B(a)P exposure on the development of cortical function, pregnant Long Evans rats were exposed to low-level B(a)P (300 microg/kg BW) by oral gavage on gestational days 14-17. At this exposure dose, there was no significant effect of B(a)P on (1) the number of pups born per litter, (2) the pre-weaning growth curves and (3) initial and final brain to body weight ratios. Control and B(a)P-exposed offspring were profiled for B(a)P metabolites in plasma and whole brain during the pre-weaning period. No detectable levels of metabolites were found in the control offspring. However, a time-dependent decrease in total metabolite concentration was observed in B(a)P-exposed offspring. On PND100-120, cerebrocortical mRNA expression was determined for the glutamatergic NMDA receptor subunit (NR2B) in control and B(a)P-exposed offspring. Neural activity was also recorded from neurons in primary somatic sensory (barrel) cortex. Semiquantitative PCR from B(a)P-exposed offspring revealed a significant 50% reduction in NR2B mRNA expression in B(a)P-exposed offspring relative to controls. Recordings from B(a)P-exposed offspring revealed that N-methyl-d-aspartate (NMDA) receptor-dependent neuronal activity in barrel cortex evoked by whisker stimulation was also significantly reduced (70%) as compared to controls. Analysis showed that the greatest deficit in cortical neuronal responses occurred in the shorter latency epochs from 5 to 20 ms post-stimulus. The results suggest that in utero exposure to benzo(a)pyrene results in diminished mRNA expression of the NMDA NR2B receptor subunit to result in late life deficits in cortical neuronal activity in the offspring. The findings from this study lead to a strong prediction that in utero exposure to benzo(a)pyrene at a time when synapses are first formed and adjusted in strength by activity in the sensory pathways will produce a strong negative effect on brain function in offspring progeny.

Stimulus frequency processing in awake rat barrel cortex.

In awake rats, we examined the relationship between neural spiking activity in primary somatic sensory cortex and the frequency of whisker stimulation. Neural responses were recorded extracellularly in barrel cortex while single whiskers were deflected with 0.5-18 air puffs per second (apps), a range that includes the whisk rates observed when rats explore their environment and discriminate surfaces with their whiskers. Twenty-nine neurons in layers III and IV were isolated in three rats (23 in barrel columns and 6 in septum columns). At < or = 9 apps, cortical neurons responded with one to two spikes per stimulus, whereas at > 9 apps, the response efficacy was reduced to only 0.2-0.4 spikes per stimulus. Several mechanisms are discussed that could account for the decrement in responsiveness. Despite this adaptation, neural spike rates increased in direct proportion with stimulus frequency when cast on logarithmic scales. At > 9 apps, however, this relationship deteriorated in barrel columns in which the response approximately halved. In contrast, septum column cells continued to increase their spike rates linearly up to 18 apps, although they responded at lower magnitude than the barrel column cells. Our findings suggest that septum column neurons are potential candidates to encode stimulus frequency using spike rate across the entire frequency range relevant to rats' whisking behavior.

Optic nerve transection affects development and use-dependent plasticity in neocortex of the rat: Quantitative acetylcholinesterase imaging.

We investigated the effects of neonatal optic nerve transection on cortical acetylcholinesterase (AChE) activity in hooded rats during postnatal development and following behavioral manipulation after weaning. AChE reaction product was quantified on digitized images of histochemically stained sections in layer IV of primary somatic sensory, primary visual and visual association cortex. Rats with optic nerve transection were compared to sham-operated littermates. In all cortical regions of both types of animal, AChE reaction product was increased to peak 2 weeks after birth and decreased thereafter, reaching adult levels at the end of the third postnatal week. During postnatal development, reaction product in primary visual cortex was lower in rats deprived of retinal input than in sham-operated littermates and the area delineated by reaction product was smaller. However, optic nerve transection did not modify the time course of postnatal development or statistically significantly diminish adult levels of AChE activity. Behavioral manipulations after weaning statistically significantly increased enzyme activity in sham-operated rats in all cortical areas examined. Compared with cage rearing, training in a discrimination task with food reward had a greater impact than environmental enrichment. By contrast, in the rats with optic nerve transection enrichment and training resulted in statistically significantly increased AChE activity only in lateral visual association cortex. Our findings provide evidence for intra- and supramodal influences of the neonatal removal of retinal input on neural activity- and use-dependent modifications of cortical AChE activity. The laminar distribution of the AChE reaction product suggests that the observed changes in AChE activity were mainly related to cholinergic basal forebrain afferents. These afferents may facilitate the stabilization of transient connections between the somatic sensory and the visual pathway.

Gestational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure effects on sensory cortex function.

Gestational exposure to environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poses a significant threat to normal growth and differentiation of the developing brain. To characterize the impact of gestational TCDD exposure on subsequent cortical function, pregnant Long Evans rats were exposed to a single acute dose (100 or 700ng/kg b.w. via gavage) on gestational day 15. This dosing regimen had no significant effect on birth index. After the TCDD-exposed animals were born and reached maturity, neural activity was recorded under urethane anesthesia from neurons in primary somatic sensory cortex. Spontaneous activity was reduced by approximately 50% in barrel cortex compared to corn oil vehicle controls. The magnitude of neuronal response to sensory (whisker) stimuli also was significantly reduced, and responses did not achieve control levels at any stimulus intensity. The greatest deficit was in the short latency component of the cortical responses. These decrements in cortical responsiveness were present in young F1 generation TCDD-exposed animals and persisted for up to 180 days. Because glutamate receptors are crucial to the evoked responses and show developmental regulation, selected iontotropic glutamate receptor subunits (NMDA NR2A+NR2B and GluR1) were profiled for RNA levels in the cortex of F1 generation rats. The expression of NR2B (NMDA receptor) and GluR1 (AMPA receptor) subunits was significantly reduced in the TCDD-exposed F1 generation animals compared to vehicle controls. The results indicate that gestational TCDD exposure results in cortical deficits that are paralled by diminished expression of certain NMDA and AMPA receptor subunits at a time when synapses are being formed for the first time in cortex.

Lesions of mature barrel field cortex interfere with sensory processing and plasticity in connected areas of the contralateral hemisphere.

Lesions of primary sensory cortex produce impairments in brain function as an outcome of the direct tissue damage. In addition, indirect lesion effects have been described that consist of functional deficits in areas sharing neural connections with the damaged area. The present study characterizes interhemispheric deficits produced as a result of unilateral lesions of the entire vibrissa representation of S-I barrel field cortex (BFC) in adult rats using single-neuron recording under urethane anesthesia. After unilateral lesions of adult BFC, responses of neurons in the contralateral homotopic BFC are severely depressed. Background (spontaneous) activity is reduced by approximately 80%, responses to test stimuli applied to the whiskers are reduced by approximately 50%, and onset of synaptic plasticity induced by trimming all but two whiskers ("whisker-pairing plasticity") is delayed over sevenfold compared with sham-lesion control animals. These deficits persist with only slight improvement for at least 4 months after lesion. Both fast-spiking and regular-spiking neuron responses are diminished contralateral to the lesion, as are cells above, below, and within the cortical barrels. Enriched environment experience increased the magnitude of responses and accelerated the rate of synaptic plasticity but did not restore response magnitude to control levels. Deficiencies in evoked responses and synaptic plasticity are primarily restricted to areas that share direct axonal connections with the lesioned cortex, because equivalently sized lesions of visual cortex produce minimal deficits in contralateral BFC function. These results indicate that interhemispheric deficits consist of remarkable and persistent decrements in sensory processing at the single-neuron level and support the idea that the deficits are somehow linked to the shared neural connections with the area of brain damage.

Experience-dependent plasticity is impaired in adult rat barrel cortex after whiskers are unused in early postnatal life.

The capacity of adult barrel cortex to show experience-dependent plasticity after early restricted neonatal sensory deprivation was analyzed in barrel field cortex neurons. Selective sensory deprivation was induced by trimming two whiskers from postnatal day 0 (P0) to P21, namely, the principal D2 whisker plus one adjacent surround whisker (D3). At maturity (P90), responses of supragranular (layer II/III) and barrel (layer IV) neurons, all located in the D2 barrel column, were analyzed for modified responses to the deprived principal whisker (D2) and the nondeprived (D1) and deprived (D3) adjacent surround whiskers. For supragranular neurons, the responses to both principal and surround whiskers were reduced at maturity, whereas the barrel neurons showed mildly elevated responses to the principal whisker but a reduced response to the deprived surround whisker. In normal adult rats, trimming all but the principal D2 whisker and an adjacent D3 whisker for 3 d (whisker pairing) produced the expected bias: elevated responses from the intact D3 compared with the cut D1 whisker in both barrel and supragranular neurons. When the neonatally deprived D2 and D3 whiskers were paired at maturity, a similar D3/D1 bias was generated in barrel neurons, but no bias occurred in supragranular neuron responses. Pairing the maintained D1 and deprived D2 whiskers produced a much greater bias toward D1 compared with the deprived D3 whisker in barrel neurons than in supragranular neurons. There were minimal effects on response latencies in layer IV under any of the experimental conditions. These findings indicate that a restricted period of sensory deprivation in early postnatal life (1) impairs intracortical relay of deprived inputs from layer IV to layer II/III in barrel cortex at maturity and (2) degrades receptive field plasticity of the supragranular layer cells but not the thalamic-recipient barrel neurons.

Rapid plasticity follows whisker pairing in barrel cortex of the awake rat.

Synaptic plasticity can be induced easily throughout life in the rodent somatic sensory cortex. Trimming all but two whiskers on one side of an adult rat's face, called 'whisker pairing', causes the active (intact) whiskers to develop a stronger drive on cortical cells in their respective barrel columns, while inactive (trimmed) whisker efficacy is down-regulated. To date, this type of activity-dependent plasticity has been induced by trimming all but two whiskers, letting the rats explore their environment from 1 day to 1 month, after which cortical responses were analyzed physiologically under anesthesia. Such studies have enhanced our understanding of cortical plasticity, but the anesthesia complicates the examination of changes that occur in the first few hours after whisker trimming. Here we assayed the short-term changes that occur in alert, active animals over a period of hours after whisker trimming. The magnitude of barrel cortex evoked responses was measured in response to stimulation of the cut and paired whiskers of rats under several conditions: (a) whisking in air (control), (b) active whisking of an object by the rat, and (c) epochs of passive whisker stimulation to identify the onset of whisker pairing plasticity changes in cortex. The main difference between whisking in air without contact and passive whisker stimulation is that the former condition induces an increased response to stimulation of inactive cut whiskers, while the latter condition increases the responses to the stimulated whiskers. The results support the conclusion that whisker pairing plasticity in barrel cortex occurs within 4 h after whisker trimming in an awake, alert animal.

Balancing bilateral sensory activity: callosal processing modulates sensory transmission through the contralateral thalamus by altering the response threshold.

Rats tactually explore a nearly spherical space field around their heads with their whiskers. The information sampled by the two sets of whiskers is integrated bilaterally at the cortical level in an activity dependent manner via the corpus callosum. We have recently shown that sensory activity in one barrel field cortex (BFC) modulates the processing of incoming sensory information to the other BFC. Whether interhemispheric integration is dynamically linked with corticothalamic modulation of incoming sensory activity is an important hypothesis to test, since subcortical relay neurons are directly modulated by cortical neurons through top-down processes. In the present study, we compared the direct sensory responses of single thalamic relay neurons under urethane anesthesia before and after inactivating the BFC contralateral to a thalamic neuron. The data show that silencing one BFC reduces response magnitude in contralateral thalamic relay neurons, significantly and reversibly, in response to test stimuli applied to the principal whisker at two times response threshold (2T) intensity for each unit. Neurons in the ventral posterior medial (VPM) nucleus and the medial division of the posterior nucleus (POm) react in a similar manner, although POm neurons are more profoundly depressed by inactivation of the contralateral BFC than VPM neurons. The results support the novel idea that the subcortical relay of sensory information to one hemisphere is strongly modulated by activity levels in the contralateral as well as in the ipsilateral SI cortex. The mechanism of the modulation appears to be based on shifting the stimulus-response curves of thalamic neurons, thereby rendering them more or less sensitive to sensory stimuli. We conclude that global sensory processing is created by combining activity in each cerebral hemisphere and continually balancing the flow of information to cortex by adjusting the responsiveness of ascending sensory pathways.

Rate code and temporal code for frequency of whisker stimulation in rat primary and secondary somatic sensory cortex.

We recorded responses to frequencies of whisker stimulation from 479 neurons in primary (S1) and secondary (S2) somatic sensory cortex of 26 urethane-anesthetized rats. Five whiskers on the right side of the snout were deflected with air puffs at seven frequencies between 1 and 18/s. In left S1 (barrels and septa) and S2, subsets of neurons (5%) responded to whisker stimulation across the entire range of frequencies with > or = 1 electrical discharges/ten stimuli (full responders). In contrast, 60% of the recorded cells responded above threshold only at stimulus frequencies below 6/s and 35% remained subthreshold at all frequencies tested. Thus, the full responders are unique in that they were always responsive and appeared particularly suited to facilitate a dynamic, broadband processing of stimulus frequency. Full responders were most responsive at 1 stimulus/s, and showed greatest synchrony with whisker motion at 18 stimuli/s. The barrel cells responded with the greatest temporal accuracy between 3 and 15 stimuli/s. The septum cells responded less accurately, but maintained their accuracy at all frequencies. Only septum cells continued to increase their discharge rate with increasing stimulus frequency. The S2 cells discharged with lowest temporal accuracy modulated only by stimulus frequencies < or = 6/s and exhibited the steepest decrease in discharge/stimulus with increasing stimulus frequency. Our observations suggest that full responders in the septa are well suited to encode high frequencies of whisker stimulation in timing and rate of discharge. The barrel cells, in contrast, showed the strongest temporal coding at stimulus frequencies in the middle range, and S2 cells were most sensitive to differences in low frequencies. The ubiquitous decline in discharge/stimulus in S1 and S2 may explain the decrease in blood flow observed at increasing stimulus frequency with functional imaging.

A combined deficiency of vitamins E and C causes severe central nervous system damage in guinea pigs.

A short period of combined deficiency of vitamins E and C causes profound central nervous system (CNS) dysfunction in guinea pigs. For this report, CNS histopathology was studied to define the nature and extent of injury caused by this double deficiency. Weanling guinea pigs were fed a vitamin E-deficient or -replete diet for 14 d. Then vitamin C was withdrawn from the diet of some guinea pigs. Four diet groups were thus formed: replete, vitamin E deficient, vitamin C deficient, and both vitamin E and C deficient. From 5 to 11 d after institution of the doubly deficient diet, 9 of 12 guinea pigs developed paralysis, and 2 more were found dead. The remaining guinea pig in the doubly deficient group and all animals in the other 3 groups survived without clinical impairment until the experiment was terminated at 13-15 d. Brains and spinal cords were serially sectioned and stained for examination. Only the combined deficiency produced damage in the CNS. The damage consisted mainly of nerve cell death, axonal degeneration, vascular injury, and associated glial cell responses. The spinal cord and the ventral pons in the brainstem were most severely affected, often exhibiting asymmetric cystic lesions. Several features of the lesions suggest that the primary damage was to blood vessels. These results indicate that the paralysis and death caused by combined deficiency of vitamins E and C in guinea pigs is caused by severe damage in the brainstem and spinal cord.