Electrophysiological studies designed to determine the geometry of spatial frequency (SF) preference in primate primary visual cortex (V1) have reported either columnar or laminar differences. In this study we used optical imaging to examine the cortical organization of SF preference in bush babies and owl monkeys using sine wave gratings of a range of SFs at 4 orientations. Both species are nocturnal but owl monkeys have a cutoff behavioral acuity of 10 c/deg whereas bush babies have a cutoff acuity of 5 c/deg. In spite of these behavioral differences both species showed the same basic tangential organization of SF preference within V1. As expected, the range of SFs close to the area centralis was shifted to higher SFs in comparison to the range of SFs seen at more eccentric locations. Examination of the activation patterns produced by the extremes of the SF range showed that these were different and revealed clusters of activation within neighboring territories. In some regions, however, high and low SFs overlapped. Iso-SF domains were generally smaller and had a different appearance than iso-orientation domains, although color-coded maps of SF preference did reveal pinwheel-like structures in some regions in both species. Comparison of maps of SF and orientation preference in the same animal suggested that these maps are largely independent. Our data supports a V1 model in which spatial frequency is mapped continuously across cortex in the form of multiple SF processing domains. (Supported by EY01778, S10RR13947, EY08126, HD15052)

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.

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 ≤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.

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 ≥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 ≤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.

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Functional magnetic resonance imaging (fMRI) has evolved into a method widely used to map neural activation in the human brain. fMRI is a method for recording blood oxygen level-dependent (BOLD) signals. These signals change with local cerebral blood flow coupled to neural activity. However, the relationship between BOLD signals and neural function is poorly understood and requires the development of animal models. Here we use an unanesthetized rat preparation to study BOLD responses to whisker stimulation in somatic sensory barrel cortex. Five rats were trained to tolerate restraint in a holder and fMRI noise with positive reinforcement. For maximal immobilization, the head was fastened to the holder with nuts screwed on threaded bolts attached to the head. On scanning day, residual stress was alleviated with injections of diazepam, and the rats were restrained in the holder and transferred into the scanner. After >75 min to allow the tranquilization to abate, structural images were acquired from three coronal brain slices. Subsequently, functional images were taken utilizing 4-min epochs without stimulation alternated with equivalent epochs during which the right caudal whiskers were stimulated with three air puffs/s. After 4 weeks, fMRI could be repeated in four rats. In seven of the nine functional runs, head motion was minimal and whisker stimulation resulted in a statistically significant (P ≤ 0.05) increase in BOLD signal in barrel cortex predominantly on the contralateral side. The results provide encouragement that long-term fMRI studies on cerebral function in unanesthetized rats may be feasible with our procedure.

Retinal and visual function returns following retinal destruction by ouabain in adult goldfish (Carassius auratus). Although the precise cellular mechanisms are unclear, the ability to regenerate CNS neurons and connections that subsequently sustain visual behavior is remarkable, especially for an adult vertebrate. In this paper, we ask whether visual stimulation via new retinal cells can activate existing cells in the optic tectum, which normally receives the largest retinal projection in this species. The right eyes of adult goldfish were injected with ouabain. After 1-18 weeks the conscious, freely moving fish were exposed to spatially and temporally varying visual stimuli and the resulting tectal metabolic activity was determined with the autoradiographic deoxyglucose method. In normal controls without lesions, visual stimulation produced equally strong metabolic activity in both tectal hemispheres, peaking in the layer where most retinotectal projections terminate (N = 6). One week after ouabain injection, metabolic activity in the contralateral, deprived tectum was dramatically reduced (N = 5), closely resembling the effect of unilateral ocular enucleation (N = 5). However, 9-18 weeks after ouabain injection, metabolic activity in the deprived tectum recovered to a level that was statistically indistinguishable from normal controls (N = 6). These findings suggest that, after a comprehensive cytotoxic lesion of the retina, regenerated ganglion cells not only establish new connections with the preexisting optic tectum, but also effectively transmit visual information they receive from newly generated photoreceptors to the "old" tectum.

Vibrissal stimulation raises cerebral blood flow (CBF) in the ipsilateral spinal and principal sensory trigeminal nuclei and contralateral ventroposteromedial (VPM) thalamic nucleus and barrel cortex. To investigate possible roles of adenosine and nitric oxide (NO) in these increases, local CBF was determined during unilateral vibrissal stimulation in unanesthetized rats after adenosine receptor blockade with caffeine or NO synthase inhibition with N-G-nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole (7-NI). Caffeine lowered baseline CBF in all structures but reduced the percent increase during stimulation only in the two trigeminal nuclei. L-NAME and 7-NI lowered baseline CBF but reduced the percent increase during stimulation only in the higher stations of this sensory pathway, i.e., L-NAME in the VPM nucleus and 7-NI in both the VPM nucleus and barrel cortex. Combinations of caffeine with 7-NI or L-NAME did not have additive effects, and none alone or in combination completely eliminated functional activation of CBF. These results suggest that caffeine-sensitive and NO-dependent mechanisms are involved but with different regional distributions, and neither fully accounts for the functional activation of CBF.

Functional magnetic resonance imaging was performed on blind adults resting and reading Braille. The strongest activation was found in primary somatic sensory/motor cortex on both cortical hemispheres. Additional foci of activation were situated in the parietal, temporal, and occipital lobes where visual information is processed in sighted persons. The regions were differentiated most in the correlation of their time courses of activation with resting and reading. Differences in magnitude and expanse of activation were substantially less significant. Among the traditionally visual areas, the strength of correlation was greatest in posterior parietal cortex and moderate in occipitotemporal, lateral occipital, and primary visual cortex. It was low in secondary visual cortex as well as in dorsal and ventral inferior temporal cortex and posterior middle temporal cortex. Visual experience increased the strength of correlation in all regions except dorsal inferior temporal and posterior parietal cortex. The greatest statistically significant increase, i.e., approximately 30%, was in ventral inferior temporal and posterior middle temporal cortex. In these regions, words are analyzed semantically, which may be facilitated by visual experience. In contrast, visual experience resulted in a slight, insignificant diminution of the strength of correlation in dorsal inferior temporal cortex where language is analyzed phonetically. These findings affirm that posterior temporal regions are engaged in the processing of written language. Moreover, they suggest that this function is modified by early visual experience. Furthermore, visual experience significantly strengthened the correlation of activation and Braille reading in occipital regions traditionally involved in the processing of visual features and object recognition suggesting a role for visual imagery.

Adult and neonatal rats were subjected to transection of the left infraorbital nerve or ablation of the left parietal cortex. The ensuing glial reaction in the whisker-to-barrel pathway was studied with immunohistochemistry for Lipocortin1- (LC1+), phosphotyrosine- (PY+), S100β- (S100β+), and mannose receptor- (MR+) immunoreactive microglia, astrocytes, and macrophages. Four days after infraorbital nerve transection in adult rats, LC1+ and PY+ microglia were prominently increased in the trigeminal sensory brain-stem nuclei on the deafferented side compared with the intact side. Changes were negligible at the second synapse of the pathway, i.e., the thalamic ventroposterior medial nucleus. Cortical ablation in adults led to an increase in microglia in the ipsilateral ventroposterior medial nucleus that reciprocally connects with the ablated cortex. Moreover, microglial reactions occurred in the contralateral trigeminal sensory brain-stem nuclei in which corticofugal projections from the ablated cortex terminate. S100β+ astrocytes, in contrast, appeared unaltered after both types of lesion in adults. In neonates, LC1+, PY+, and S100β+ cells did not have the adult morphology of microglia or astrocytes. Four days after nerve transection, LC1+ and PY+ cells were sparse and remained unchanged. In contrast, S100β+ cells substantially increased in the deafferented trigeminal brain-stem nuclei. Four days after cortical ablation in neonates, LC1+, PY+, and S100β+ cells had accumulated in the deprived thalamus. In contrast to adults, many of these cells were MR+ macrophages. In the deprived brain-stem, only S100β+ cells increased and none were macrophages. Therefore, macrophages do not appear to stem from microglia, and neonatal LC1+, PY+, and S100β+ cells may possess functions different from those in adults.

How neurons in the primary visual cortex (V1) of primates process parallel inputs from the magnocellular (M) and parvocellular (P) layers of the lateral geniculate nucleus (LGN) is not completely understood. To investigate whether signals from the two pathways are integrated in the cortex, we recorded contrast-response functions (CRFs) from 20 bush baby V1 neurons before, during, and after pharmacologically inactivating neural activity in either the contralateral LGN M or P layers. Inactivating the M layer reduced the responses of V1 neurons (n = 10) to all stimulus contrasts and significantly elevated (t = 8.15, P < 0.01) their average contrast threshold from 8.04 (± 4.1)% contrast to 22.46 (± 6.28)% contrast. M layer inactivation also significantly reduced (t = 4.06, P < 0.01) the average peak response amplitude. Inactivating the P layer did not elevate the average contrast threshold of V1 neurons (n = 10), but significantly reduced (t = 4.34, P < 0.01) their average peak response amplitude. These data demonstrate that input from the M pathway can account for the responses of V1 neurons to low stimulus contrasts and also contributes to responses to high stimulus contrasts. The P pathway appears to influence mainly the responses of V1 neurons to high stimulus contrasts. None of the cells in our sample, which included cells in all output layers of V1, appeared to receive input from only one pathway. These findings support the view that many V1 neurons integrate information about stimulus contrast carried by the LGN M and P pathways.

The follicles of whiskers C1–3 were removed from the left side of the snout of adult mice. Adjacent whiskers B1–3 and D1–3 were stimulated while local rates of glucose utilization were measured with the [14C]2-deoxyglucose method two, four, eight, 64, 160 and ∼250 days after follicle removal. Local metabolic activity in the trigeminal sensory brainstem and somatosensory thalamus was compared with that of unoperated mice with the same stimulation and of mice with the same lesion that had all whiskers clipped. Actual rates of glucose utilization were measured in brainstem subnuclei caudalis and interpolaris whereas metabolic activation was only assessable by colour-coded imaging in brainstem nucleus principalis and in the thalamic ventrobasal complex.

We investigated alterations of the metabolic whisker map of barrel cortex after the removal of the follicles of left whiskers C1, C2 and C3 in adult albino mice. The quantitative autoradiographic [C-14]deoxyglucose method was used to measure local cerebral metabolic rates for glucose in barrel cortex of mice two, four, eight, 64, 160 and 250 days after the lesion. Metabolic rates were measured in three groups of animals: (i) mice with lesions that had all whiskers clipped; (ii) mice with lesions that had left whiskers B1-3 and D1-3 stimulated; and (iii) unoperated mice that had left whiskers B1-3 and D1-3 stimulated. Compared with the metabolic rates in barrels C1-3 of stimulated unoperated mice, barrels C1-3 of stimulated mice with lesions showed the first discernible increase in metabolic rate four days after the lesion. The increase became distinct at 64 days, but attained statistical significance only similar to 160 days after the lesion. The lesion pei se, i.e. without whisker stimulation, caused only a small increase in metabolic rate in barrels C1-3 accounting for not more than one fourth of the increase in metabolic rate measured after whisker deflection. The removal of whisker follicles C1-3 led, therefore, to an enlargement of the metabolic representations of the adjacent whiskers into the barrels deprived by the lesion. The gradual consolidation of the alterations of the metabolic whisker map coincided with the regeneration of follicular nerves in the whiskerpad. We detected anomalous deep nerves innervating follicles surrounding the lesion at similar to 64 days, and the number of myelinated nerve fibres in the deep nerves of these follicles was increasing with increasing time after the lesion.The coincidence of peripheral and central change suggests that the reorganization of the innervation of the sensory periphery plays an important role in the persistent alterations of the cortical somatotopy in adults following a lesion in the sensory periphery. (C) 1997 IBRO. Published by Elsevier Science Ltd.

Transections of the infraorbital nerve in adult rats resulted in progressive alterations of microglia identified by Lipocortin1 immunoreactivity at the sites where the primary afferents terminate, i.e. in the trigeminal brainstem sensory nuclei. Microglia proliferated three- to four-fold. Their cell bodies enlarged and their processes thickened. Microglial responses were similar to the removal of whisker follicles. However. they were restricted to discrete nuclear subregions that matched with the known whisker somatotopy. Astrocytes identified by S100 beta immunoreactivity showed minor increases in size and in population density. No microglial or astrocytic reactions were found in the second and third synaptic relays of the somatosensory pathway.Because both types of lesion reportedly lead to the reorganization of primary afferents, our results establish the two experimental designs as valuable tools to elucidate the role of microglia and Lipocortin1 in adult brain plasticity. (C) 1997 IBRO. Published by Elsevier Science Ltd.

Using in situ hybridization histochemistry, we investigated the effects of whisker stimulation in freely moving rats on the expression of the immediate-early genes zif 268 and c-fos in the barrel cortex. Whiskers equipped with metal filaments were stimulated for 5-15 minutes with a pulsating magnetic field. Such whisker stimulation resulted in increased zif 268 and c-fos expression that was largely restricted to radial columns across the barrels representing the stimulated whiskers. In these columns, gene expression was elevated, to a variable degree, across the entire cortical thickness, with a distinct maximum in layer IV. The magnitude of gene expression in a barrel was proportional to the intensity of stimulation. Cellular analysis confirmed that whisker stimulation induced c-fos expression mostly in stellate cells of layer IV and in some pyramidal cells in other layers. However, even after the strongest stimulation, only subsets of neurons were labeled in all layers, suggesting that subpopulations of neurons with a differential genomic response to sensory input exist. These results indicate that the expression of these immediate-early genes is regulated by normal neuronal activity under physiological conditions, and suggest that such gene regulation is an integral part of neuronal function.

We employed the autoradiographic deoxyglucose method to study metabolic whisker maps of the adult mouse somatosensory brainstem and thalamus after the neonatal removal of left whisker follicles C1, C2 and C3. Left whiskers B1-3 and D1-3 were deflected to metabolically activate the somatosensory pathway. Unoperated mice that were stimulated in the same fashion served as controls, Whisker stimulation resulted in an ipsilateral increase in metabolic activity in the three trigeminal brainstem structures in which the whiskers are represented topologically by segments of high cytochrome oxidase activity, i.e. subnucleus caudalis, subnucleus interpolaris and nucleus principalis. In the two subnuclei of mice with lesions and of controls, there was an increase in metabolic activity of the representations of the deflected whiskers, whereas the metabolic activity of representations A1-3 and E1-3 was low. Apart from these similarities, the metabolic activation of the representations originally representing whiskers C1-3 was remarkably greater in mice with lesions than in controls. This increase reached statistical significance in subnucleus caudalis and approached statistical significance in subnucleus interpolaris. In nucleus principalis the deprived territory was only partially activated and the degree of metabolic activation was less than in the subnuclei. In the thalamic ventrobasal complex of mice with lesions metabolic activity was unpatterned whereas two areas of metabolic activation were distinct in controls. Hence, the removal of whisker follicles in newborn mice resulted in the suppression of localized metabolic responses to whisker stimulation in the thalamus, whereas in the brainstem stimulus-related activity was prominent and the deprived territory became responsive to the stimulation of whisker follicles adjacent to the lesion. Apparently, the modification of the whisker representation at the first synapse of the pathway induces a diminution of localized responsivity in the thalamus.