Widespread activation of barrel cortex by small numbers of neonatally spared whiskers

Activity-dependent plasticity in rodent whisker barrel cortex was examined by means of high-resolution 2-deoxyglucose (2-DG) with immunohistochemical double labeling. Hamsters with all but one, two, or four follicles ablated on postnatal day 7 received 2-DG injections as adults. Autoradiograms of follicle-ablated animals showed heavy activation of the entire barrel field during normal behavior, despite the missing whiskers. The intensity of 2-DG labeling was significantly reduced if the whiskers spared after follicle ablation were trimmed prior to the 2-DG injection, demonstrating that the widespread activation was driven by the spared whiskers. This widespread metabolic activation of the adult barrel field after neonatal follicle ablation was in sharp contrast to the somatotopically appropriate 2-DG labeling in barrel fields of normal adults subject to acute trimming of most whiskers, but was similar to that seen in normal adult animals with all whiskers intact. The results demonstrate large-scale plasticity of barrel circuitry following neonatal sensory deprivation, and provide a powerful functional anatomical setting to investigate underlying mechanisms.     

The activation of cannabinoid receptors in striatonigral GABAergic neurons inhibited GABA uptake

Cannabinoid receptors (CNRs) in basal ganglia are located on striatal efferent neurons which are gamma-aminobutiric acid (GABA)-containing neurons. Recently, we have demonstrated that CN-induced motor inhibition is reversed by GABA-B, but not GABA-A, receptor antagonists, presumably indicating that the activation of CNRs in striatal outflow nuclei, mainly in the substantia nigra, should be followed by an increase of GABA concentrations into the synaptic cleft of GABA-B receptor synapses. The present study was designed to examine whether this was originated by increasing GABA synthesis and/or release or by decreasing GABA uptake. We analyzed: (i) GABA synthesis, by measuring the activity of glutamic acid decarboxylase (GAD) and GABA contents in brain regions that contain striatonigral GABAergic neurons, after in vivo administration of CNs and/or the CNR antagonist SR141716; (ii) [3H]GABA release in vitro in the presence or the absence of a synthetic CN agonist, HU-210, by using perifusion of small fragments of substantia nigra; and (iii) [3H]GABA uptake in vitro in the presence or the absence of WIN-55,212-2, by using synaptosomes obtained from either globus pallidus or substantia nigra. Results were as follows. Delta9-tetrahydrocannabinol (delta9-THC) and HU-210, did not alter neither GAD activity nor GABA contents in both the striatum and the ventral midbrain at any of the two times tested, thus suggesting that CNs apparently failed to change GABA synthesis in striatonigral GABAergic neurons. A similar lack of effect of HU-210 on in vitro [3H]GABA release, both basal and K+-evoked, was seen when this CN was added to perifused substantia nigra fragments, also suggesting no changes at the level of GABA release. However, when synaptosome preparations obtained from the substantia nigra were incubated in the presence of WIN-55,212-2, a decrease in [3H]GABA uptake could be measured. This lowering effect was specific of striatonigral GABAergic neurons since it was not observed in synaptosome preparations obtained from the globus pallidus. In summary, the activation of CNRs located on striatonigral GABAergic neurons, which primarily access to GABA-B receptor synapses, was accompanied by a reduction in neurotransmitter uptake, thus prolonging the presence of GABA into the synaptic cleft. This mechanism might underly the CN-induced motor inhibition through the potentiation of the inhibitory effect of GABA on neuronal activity, in particular of nigrostriatal dopaminergic neurons.     

Innervation of VIP-immunoreactive neurons by the ventroposteromedial thalamic nucleus in the barrel cortex of the rat

We investigated the synaptic terminals of fibers originating in the ventroposteromedial thalamic nucleus (VPM) and projecting to the main input layers (IV/III) of the rat posteromedial barrel subfield. It was our aim to determine whether or not the subpopulation of vasoactive intestinal polypeptide (VIP)-immunoreactive neurons in these layers are directly innervated by the sensory thalamus. Anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and immunohistochemistry for VIP were combined for correlated light and electron microscopic examination. Columns of cortical tissue were well defined by barrel-like patches of PHA-L-labeled fibers and boutons in layers IV and III. Within these columns VIP-immunoreactive perikarya were located mainly in supragranular layers. Marked perikarya were also seen in infragranular layers, but their immunoreactivity was often weaker. Granular layer IV, which is the main terminal field for thalamic fibers, contained fewer VIP neurons than supragranular layers. In the light microscope, however, PHA-L-labeled fibers appeared to contact the somata or proximal dendrites of 60-86% of the layer IV VIP neurons . By contrast, only 18-35% of the VIP neurons in the supragranular layers, which receive a moderately dense projection from the VPM, appeared to be contacted. PHA-L-labeled boutons were seen close to 13-25% of infragranular VIP-positive cells. Electron microscopy showed that thalamic fibers formed at most four asymmetric synapses on a single layer IV, VIP-positive neuron. Although the proportion of VIP-positive neurons with labeled synapses was lower in supragranular layers, most of them shared multiple asymmetric synapses with labeled thalamic fibers. Up to six labeled synapses were seen on individual VIP neurons in layer III. We conclude that subpopulations of VIP-immunoreactive neurons, located in layers IV, III, and II are directly innervated by the VPM. These neurons may be involved in the initial stages of cortical processing of sensory information from the large, mystacial vibrissae. Since VIP is known to be colocalized with the inhibitory transmitter GABA, it is likely that VIP neurons participate in the shaping of the receptive fields in the barrel cortex.     

Experience-dependent plasticity in adult rat barrel cortex

This study tested the hypothesis that the receptive fields (RFs) of neurons in the adult sensory cortex are shaped by the recent history of sensory experience. Sensory experience was altered by a brief period of "whisker pairing": whiskers D2 and either D1 or D3 were left intact, while all other whiskers on the right side of the face were trimmed close to the fur. The animals were anesthetized 64-66 h later and the responses of single neurons in contralateral cortical barrel D2 to stimulation of whisker D2 (the center RF) and the four neighboring whiskers (D1, D3, C2, and E2; the excitatory surround RF) were measured. Data from 79 cells in four rats with whiskers paired were compared to data from 52 cells in four rats with untrimmed whiskers (control cases). During the period of whisker pairing, the RFs of cells in barrel D2 changed in three ways: (i) the response to the center RF, whisker D2, increased by 39%, (ii) the response to the paired surround RF whisker increased by 85-100%, and (iii) the response to all clipped (unpaired) surround RF whiskers decreased by 9-42%. In the control condition, the response of barrel D2 cells to the two neighboring whiskers, D1 and D3, was equal. After whisker pairing, the response to the paired neighbor of D2 was more than twice as large as the response to the cut neighbor of D2. These findings indicate that a brief change in the pattern of sensory activity can alter the configuration of cortical RFs, even in adult animals.     

An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons

Olfactory sensory neurons expressing a given odorant receptor project to two topographically fixed glomeruli in the olfactory bulb. We have examined the contribution of different cell types in the olfactory bulb to the establishment of this topographic map. Mice with a homozygous deficiency in Tbr-1 lack most projection neurons, whereas mice with a homozygous deficiency in Dlx-1 and Dlx-2 lack most GABAergic interneurons. Mice bearing a P2-IRES-tau-lacZ allele and deficient in either Tbr-1 or Dlx-1/Dlx-2 reveal the convergence of axons to one medial and one lateral site at positions analogous to those observed in wild-type mice. These observations suggest that the establishment of a topographic map is not dependent upon cues provided by, or synapse formation with, the major neuronal cell types in the olfactory bulb.     

Analysis of the spike activity of neurons of the orbital cortex of rabbits during feeding behavior

Computer analysis of statistical characteristics (mean interspike interval, mean frequency of discharges, standard deviation, variation coefficient, coefficients of serial correlation and histograms of interspike intervals duration) of spike activity of 31 neurones in the orbital cortex recorded in eleven experiments on six unrestrained rabbits reveals a specific reflection of the main stages of the animals' alimentary purposive behaviour.     

Intracellular Ca2+ during metabolic activation of KATP channels in spontaneously active dorsal vagal neurons in medullary slices

Intracellular Ca2+ ([Ca2+]i) and membrane properties were measured in fura-2 dialysed dorsal vagal neurons (DVN) spontaneously active at a frequency of 0.5-5 Hz. [Ca2+]i increased by about 30 nm upon rising spike frequency by more than 200% due to 20-50 pA current pulses or 10 micrometer serotonin. It fell by 30 nm upon block of spiking by current-injection, tetrodotoxin or Ni2+ and also during hyperpolarization due to gamma-aminobutyric acid or opening of adenosine triphosphate (ATP) -sensitive K+ (KATP) channels with diazoxide. KATP channel-mediated hyperpolarizations during anoxia or cyanide produced an initial [Ca2+]i decrease which reversed into a secondary Ca2+ rise by less than 100 nm. Similar moderate rises of [Ca2+]i were observed during block of aerobic metabolism under voltage-clamp as well as in intact cells, loaded with fura-2 AM. The magnitude of the metabolism-related [Ca2+]i transients did not correlate with the amplitude of the KATP channel-mediated outward current. [Ca2+]i did not change during diazoxide-induced or spontaneous activation of KATP outward current observed in 10% of cells after establishing whole-cell recording. Increasing [Ca2+]i with cyclopiazonic acid did not activate KATP channels. [Ca2+]i was not affected upon block of outward current with sulphonylureas, but these KATP channel blockers were effective to reverse inhibition of spike discharge and, thus, the initial [Ca2+]i fall upon spontaneous or diazoxide-, anoxia- and cyanide-induced KATP channel activation. A sulphonylurea-sensitive hyperpolarization and [Ca2+]i fall was also revealed in the early phase of iodoacetate-induced metabolic arrest, whereas after about 20 min, occurrence of a progressive depolarization led to an irreversible rise of [Ca2+]i to more than 1 micrometer. The results indicate that KATP channel activity in DVN is not affected by physiological changes of intracellular Ca2+ and the lack of a major perturbance of Ca2+ homeostasis contributes to their high tolerance to anoxia.     

Differential interaction between 5-HT3 receptors and GABAergic neurons inhibiting acetylcholine release in rat entorhinal cortex slices

The 5-HT3 receptor antagonists, ondansetron, MDL 72222 and granisetron (0.01-1 microM), produced a concentration-dependent increase of K+-evoked [3H]ACh efflux in slices from rat entorhinal cortex preloaded with [3H]choline. Bicuculline and flumazenil, antagonists at different sites of the GABAA receptor, also enhanced [3H]ACh efflux. While the ACh releasing effect of ondansetron was markedly potentiated, in a TTX-sensitive manner, by bicuculline, the effects of MDL 72222 and granisetron were not significantly modified. A qualitatively identical interaction was found by using flumazenil, a GABAA antagonist at the benzodiazepine recognition site, in combination with the 5-HT3 receptor antagonists. The potentiation by the GABAA antagonists of [3H]ACh efflux was also observed in a superfusion medium deficient in Cl-. The nonspecific K+-channel blockers TEA and Ba2+ also increased K+-evoked [3H]ACh efflux in this preparation but the releasing effect was not modified by bicuculline. The results support the functional interaction of ondansetron with GABAergic interneurons in the rat entorhinal cortex, GABA-independent mechanisms may however be involved in the regulation of cortical cholinergic function by other 5-HT3 receptor antagonists.     

Experience-dependent changes in function and anatomy of adult barrel cortex

Manipulations of sensory input to vibrissal mechanoreceptors can modify columnar functioning of the barrel cortex in adult animals. In mice, partial vibrissectomy sparing one row of vibrissae in young adults results 7 days later in an increase in the functional cortical column activated by the spared whiskers and visualized with 2-deoxyglucose autoradiography. The increase in the extent of the labelled area is visible in all cortical layers, but particularly in layer V, where the metabolic labelling is more intense in the representation of the spared vibrissae. Two months after vibrissectomy the enlargement of the labelled area is accentuated. Deprivation of a row of vibrissae results in a decrease in the areal extent of its cortical representation. Investigations of cortico-cortical connections carried out in living slices of the barrel cortex of mice 2 months after vibrissectomy sparing one row of whiskers, revealed elongation and increased branching of axons originating in the spared cortical column. The dendritic spine density was increased on the basal dendrites of layer V pyramidal neurons of the spared column and decreased on layer III apical dendrites of the deprived column. Thus, prolonged changes in functional activation of adult barrel cortex are accompanied by rearrangement of cortico-cortical circuitry.     

Cocaine-induced activation of striatal neurons during focused stereotypy in rats

As psychomotor stimulants, both amphetamine and cocaine elicit episodes of repetitive motor activation (focused stereotypy) known to involve the mesostriatal dopamine system. During amphetamine-induced focused stereotypy, motor-related neurons in the striatum respond with either an excitation or inhibition, depending on dose and behavioral pattern, whereas nonmotor-related units are inhibited. To assess striatal activity during the focused stereotypy induced by cocaine, both types of striatal units were recorded in ambulant rats. Either 20 or 40 mg/kg cocaine caused highly focused sniffing and head bobbing, which occurred in conjunction with activation of both motor- and nonmotor-related neurons. The activation of motor-related units was evident even when firing rate was compared during periods of matched pre- and post-drug behavior, arguing against movement as the sole basis for the drug-induced neuronal excitation. Subsequent administration of haloperidol (1.0 mg/kg) reversed but did not completely block the neuronal activation, while the behavioral response shifted away from focused stereotypy toward an increase in ambulation. Thus, the level of activation of both motor- and nonmotor-related striatal neurons may play a critical role in the behavioral response pattern induced by cocaine.     

Variability in visual cortex activation during prolonged functional magnetic resonance imaging

OBJECTIVE: To review the EEG features of ring 20 syndrome in two patients and determine the characteristic pattern of this syndrome. The features of our cases and 24 patients reported in the literature will be discussed. SUBJECTS AND METHODS: Report of two patients and review of literature. RESULTS: The two patients had intractable epilepsy since childhood. Their clinical seizures were mostly complex partial seizures. Often the patients seizures were of prolonged duration. Ictal EEG revealed characteristic slow waves, and sharp waves. The slow waves were (1) usually synchronous high-voltage slow waves with or without a spike component predominantly in the frontal and frontopolar areas, (2) sometimes showed a change in frequency every several seconds, (3) continued for a long period, and (4) easily spread diffusely. The sharp waves were 5-6 Hz irregular and diffuse discontinuous sharp waves, and sometimes appeared predominantly in the centroparietal area. The clinical seizure pattern and EEG findings were similar in the 24 published cases. CONCLUSIONS: These EEG findings may be a characteristic feature of ring 20 syndrome and thus may be useful as a diagnostic clue.     

Electrophysiological characterization of GABAergic neurons in the ventral tegmental area

GABAergic neurons in the ventral tegmental area (VTA) play a primary role in local inhibition of mesocorticolimbic dopamine (DA) neurons but are not physiologically or anatomically well characterized. We used in vivo extracellular and intracellular recordings in the rat VTA to identify a homogeneous population of neurons that were distinguished from DA neurons by their rapid-firing, nonbursting activity (19.1 +/- 1.4 Hz), short-duration action potentials (310 +/- 10 microseconds), EPSP-dependent spontaneous spikes, and lack of spike accommodation to depolarizing current pulses. These non-DA neurons were activated both antidromically and orthodromically by stimulation of the internal capsule (IC; conduction velocity, 2.4 +/- 0.2 m/sec; refractory period, 0.6 +/- 0.1 msec) and were inhibited by stimulation of the nucleus accumbens septi (NAcc). Their firing rate was moderately reduced, and their IC-driven activity was suppressed by microelectrophoretic application or systemic administration of NMDA receptor antagonists. VTA non-DA neurons were recorded intracellularly and showed relatively depolarized resting membrane potentials (-61.9 +/- 1.8 mV) and small action potentials (68.3 +/- 2.1 mV). They were injected with neurobiotin and shown by light microscopic immunocytochemistry to be multipolar cells and by electron microscopy to contain GABA but not the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH). Neurobiotin-filled dendrites containing GABA received asymmetric excitatory-type synapses from unlabeled terminals and symmetric synapses from terminals that also contained GABA. These findings indicate that VTA non-DA neurons are GABAergic, project to the cortex, and are controlled, in part, by a physiologically relevant NMDA receptor-mediated input from cortical structures and by GABAergic inhibition.     

Reaction of visual cortex neurons to cross-like figures during local inhibition blockade

Incidental finding of a primary malignant lymphoma of the ovary in a 20-year-old patient is presented. Two and a half years following ablative surgery and adjuvant chemotherapy, the patient is alive and disease free. Ovarian lymphoma is a disease of reportedly poor prognosis. However, many previously reported cases of ovarian lymphoma actually represented ovarian involvement by a more diffuse lymphomatous process. If stringent criteria are used for case selection, true primary ovarian lymphoma usually carries a favorable prognosis.     

Quantitative distribution of parvalbumin, calretinin, and calbindin D-28k immunoreactive neurons in the visual cortex of normal and Alzheimer cases

The distribution of parvalbumin (PV), calretinin (CR), and calbindin (CB) immunoreactive neurons was studied with the help of an image analysis system (Vidas/Zeiss) in the primary visual area 17 and associative area 18 (Brodmann) of Alzheimer and control brains. In neither of these areas was there a significant difference between Alzheimer and control groups in the mean number of PV, CR, or CB immunoreactive neuronal profiles, counted in a cortical column going from pia to white matter. Significant differences in the mean densities (numbers per square millimeter of cortex) of PV, CR, and CB immunoreactive neuronal profiles were not observed either between groups or areas, but only between superficial, middle, and deep layers within areas 17 and 18. The optical density of the immunoreactive neuropil was also similar in Alzheimer and controls, correlating with the numerical density of immunoreactive profiles in superficial, middle, and deep layers. The frequency distribution of neuronal areas indicated significant differences between PV, CR, and CB immunoreactive neuronal profiles in both areas 17 and 18, with more large PV than CR and CB positive profiles. There were also significantly more small and less large PV and CR immunoreactive neuronal profiles in Alzheimer than in controls. Our data show that, although the brain pathology is moderate to severe, there is no prominent decrease of PV, CR and CB positive neurons in the visual cortex of Alzheimer brains, but only selective changes in neuronal perikarya.     

Peptide gene activation, secretion, and steroid feedback during stimulation of rat neuroendocrine corticotropin-releasing hormone neurons

We have used colloid-induced hypovolemia to investigate mechanisms operating in CRH neuroendocrine neurons of the hypothalamic paraventricular nucleus during a sustained stress. Specifically, three questions have been addressed using in situ hybridization and RIA. 1) Do neuropeptide secretion and gene activation share the same stimulus threshold? 2) Does corticosterone modulate mechanisms regulating CRH gene expression during sustained stress? 3) How are neuropeptides commonly colocalized with CRH affected? Our results show that the secretion of ACTH and activation of the CRH gene have distinct and separate stimulus thresholds. The threshold is higher for CRH gene activation than for ACTH secretion, suggesting some degree of mechanistic separation. In addition, corticosterone secreted during the first 3 h of sustained hypovolemia does not inhibit CRH gene expression. However, feedback inhibition may occur in the delayed time domain. Finally, neuropeptides colocalized with CRH are differentially regulated by sustained hypovolemia. Proenkephalin messenger RNA levels show a slower temporal response than those of CRH, while the vasopressin gene is not activated at any time in parvicellular neuroendocrine neurons. Our results emphasize that CRH neuroendocrine neurons respond to a stress event in a stimulus-specific manner in terms of both the profiles of secretion and gene expression, and the structure of glucocorticoid feedback.     

Role of nitric oxide in the pancreatic vascular and metabolic responses associated with activation of capsaicin-sensitive neurons

A significant decrease in mean number of CD5+, CD8(+)-lymphocytes in persons, who worked in 30-km zone of Chernobyl nuclear power station was revealed. A significant increase in percent of CD5+, CD4(+)-cell percents was observed in workers, who worked for 1,2-2,5 years in zone, but absolute number, were decreased comparing a control and data received in people, who have just arrived to work in 30-km zone. The positive correlation exists between the percent of lymphocytes and years of service in 30-km zone. The lower level of alpha 1-thymosine was revealed in serum of the persons, who worked in zone for 4.5-5 years than data received in people, who worked for 0.5 year. Increase level of serum autoantibodies reacting with thymic epithelial cell was detected in men, who worked in zone for 3-3.5 years. In persons, who worked more 5 years and have just arrived in zone identical data were received.     

Oxidative metabolic changes, antioxidantion, and platelet activation rat phagocytes during development of experimental specific tuberculous changes

Efficacy and possibility of direct operations on the macular area of the retina in humid (exudative) maculopathies (senile maculodystrophy) is validated theoretically, morphologically, and clinically. A hypothesis on the mechanism of exudative process development in the macular area in degenerative diseases is formulated on the basis of pathohistological analysis of removed subpigmental material. Indications for such operations are defined.     

Development of the barrels and barrel field in the somatosensory cortex of the mouse

Barrels of the PMBSF of the mouse somatosensory cortex become apparent in Nissl-stained tangential sections simultaneously, on the fourth postnatal day. At this time they are miniatures of those in the adult and are situated in the deepest sublamina of the trilaminar cortical plate. An early barrel appears as a patch of decreased cell density: the prospective hollow of the barrel. Septa become noticeable during the sixth postnatal day. From that period to adulthood, the relative contribution of the PMBSF to the total cortical surface area increases -- an increase that goes against one's expectation: the barrel related periphery matures very early and so does the central, lateral region of the cortex. Barrel growth parallel to the pial surface is greater along the major axes than along the minor axes. By using the barrels to identify prospective layer IV in immature cortex, we could determine that layers V and VI attain their adult height during the sixth postnatal day -- an age when prospective layers I-IV are only half their adult height. The onset of barrel formation coincides with the moment after which injury to the pertinent somatosensory periphery (the vibrissal papillae) no longer causes profound alterations in barrel morphology.