Somatosensory Cerebral Cortex Research Articles

Neuroprotective properties of GABA and its derivatives in diabetic encephalopathy in old animals

The aim of the work was to evaluate the GABA neuroprotective properties and its structural analogues in old animals after seven months of hyperglycemia.Materials and methods. Diabetes mellitus was modeled in white outbred male rats (12 months old) by the administration of a streptozotocin (65 mg/kg) and nicotinamide (230 mg/kg) combination. After 6 months, the animals with a postprandial glycemia level between 11 and 18 mmol/l were selected for the study. After the groups had been formed, the animals were administrated with GABA and GABAergic compounds (Compositions МРВАand PPC), respectively, for 1 month, the control group animals were administrated with saline. After the treatment, an oral glucose tolerance test and a set of behavioral tests aimed at studying sensory-motor (Open Field, Adhesion test, Rotarod) and cognitive functions (New Object Recognition and Morris Water Maze), as well as the functional state evaluation of the endothelium were performed. Further on, sampling of blood and brain tissues for a biochemical and enzyme immunoassay (the level of glucagon-like peptide-1 (GLP-1) and TNF-α in serum and the level of Klotho protein, BDNF, Nrf2, NF-κB and malondialdehyd (MDA) in brain homogenates), as well as a morphological analysis of changes in CA1 and CA3 neurons of the hippocampus and somatosensory cortex, was carried out.Results. GABA and compositions with its derivatives had a pronounced neuroprotective effect in old animals with prolonged hyperglycemia. The hypoglycemic effect of the studied compositions was accompanied by an increase in the production of GLP-1. In the animals with DM, after 6 weeks of the test substances administration, higher rates of sensory-motor and cognitive functions and a less structural damage to the sensory-motor cortex and the brain hippocampus were recorded. These effects may be due to higher levels of the Klotho proteins, Nrf2 and BDNF, as well as lower levels of NF-κB, which may underlie the suppression of the oxidative stress, the reduction of MDA and inflammation (TNF-α).Conclusion. After 6 weeks of the administration, GABA and its compositions in old animals (19 months old) significantly improved sensory-motor and cognitive functions, reduced negative structural changes in the hippocampus and somatosensory cerebral cortex.

Some Features of Contact Formation between Сhemical Synapse and Astrocytes Membrane in the Primary Somatosensory Сerebral Сortex of Rats

Introduction. The contact point between an astrocyte and a chemical synapse is the location of the signaling and transport processes that play an important role in functioning of the nervous system and in neurological diseases pathogenesis of humans and animals. The goal of the study was to investigate the correlation between the average size of the active zone of the synapse and the frequency of synapse-astrocyte contact formation in the cerebral cortex layers of rats.Materials and methods. The 40 μm frontal sections of the primary somatosensory cortex of 5 outbred male white rats were taken as the material for the study. Astrocytes were labelled for Transmission Electron Microscopy (TEM) by incubation of the tissue sections with primary antibodies to the s100β protein and with horseradish peroxide-conjugated secondary antibodies, followed by the development of the label in the reaction with DAB. For each layer, 250 images were obtained at 25,000х magnification. On the images the length of the synaptic cleft was measured and the number of synapses forming contact with the astrocyte membrane was counted.Results. The value of the fraction of the chemical synapses forming contact with the astrocyte membrane in the primary somatosensory cerebral cortex of rats demonstrated the direct correlation with the average length of the synaptic cleft only in the first to fourth layers. Thus, in the first layer, the value of the fraction of synapses forming contact with the astrocyte was the smallest (PI = 0.27 ± 0.1), as was the length of the synaptic cleft (lI = 329.45 ± 10.45). When moving deeper into the cortex, the fraction of synapses forming contact with the astrocyte and the length of the synaptic cleft increased from the second (PII = 0.48 ± 0.11 and lII = 363.64 ± 11.14) to the third layer (PIII = 0.69 ± 0.09 and lIII = 382.27 ± 9.81), followed by the decrease of both values in the fourth layer (PIV = 0.53 ± 0.09 and lIV = 355.2 ± 8.12). In the fifth layer, the fraction of synapses forming contact with the astrocyte sharply increased again (PV = 0.68 ± 0.08), which, however, was not accompanied by the proportional increase of the average length of the synaptic cleft (lV = 350.79 ± 7.82). At the same time, in the sixth layer of the cortex, on the contrary, the sharp increase in the average length of the synaptic cleft (lVI = 396.03 ± 10.77) was observed, reaching the maximum value through the cortex, with low, compared to other layers, fraction of synapses forming contact with the astrocyte (PVI = 0.44 ± 0.09). Thus, it turned out that the fraction of synapses forming contact with the astrocytic membrane is more related to the density of the astrocytic membranes in the layer (the research we published earlier), rather than to the average length of the synaptic cleft. Discussion and conclusions. The obtained results substantiate that the contact is formed as a result of a combination of random membranes encounter followed by the selective anchoring or repulsion of the astrocyte membrane under the influence of various factors, only partly determined by the size of the chemical synapse.

The Correlation of Neuronal Signals with Behavior at Different Levels of Visual Cortex and Their Relative Reliability for Behavioral Decisions.

Behavior can be guided by neuronal activity in visual, auditory, or somatosensory cerebral cortex, depending on task requirements. In contrast to this flexible access of cortical signals, several observations suggest that behaviors depend more on neurons in later areas of visual cortex than those in earlier areas, although neurons in earlier areas would provide more reliable signals for many tasks. We recorded from neurons in different levels of visual cortex of 2 male rhesus monkeys while the animals did a visual discrimination task and examined trial-to-trial correlations between neuronal and behavioral responses. These correlations became stronger in primary visual cortex as neuronal signals in that area became more reliable relative to the other areas. The results suggest that the mechanisms that read signals from cortex might access any cortical area depending on the relative value of those signals for the task at hand.SIGNIFICANCE STATEMENT Information is encoded by the action potentials of neurons in various cortical areas in a hierarchical manner such that increasingly complex stimulus features are encoded in successive stages. The brain must extract information from the response of appropriate neurons to drive optimal behavior. A widely held view of this decoding process is that the brain relies on the output of later cortical areas to make decisions, although neurons in earlier areas can provide more reliable signals. We examined correlations between perceptual decisions and the responses of neurons in different levels of monkey visual cortex. The results suggest that the brain may access signals in any cortical area depending on the relative value of those signals for the task at hand.

Ketamine reduces remifentanil-induced postoperative hyperalgesia mediated by CaMKII-NMDAR in the primary somatosensory cerebral cortex region in mice

Remifentanil is commonly used clinically for perioperative pain relief, but it may induce postoperative hyperalgesia. Low doses of ketamine have remained a common choice in clinical practice, but the mechanisms of ketamine have not yet been fully elucidated. In this study, we examined the possible effects of ketamine on calcium/calmodulin-dependent protein kinase II α (CaMKIIα) and N-methyl-d-aspartate receptor (NMDAR) subunit NR2B in a mouse model of remifentanil-induced postoperative hyperalgesia (RIPH) in the primary somatosensory cerebral cortex (SI) region. The paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were used to assess mechanical allodynia and thermal hyperalgesia, respectively, before and after intraoperative remifentanil administration. Before surgery, mice received intrathecal injections of the following drugs: ketamine, NMDA, BayK8644 (CaMKII activator), and KN93 (CaMKII inhibitor). Immunofluorescence was performed to determine the anatomical location and expression of activated CaMKIIα, phosphorylated CaMKIIα (p-CaMKIIα). Additionally, western blotting was performed to assess p-CaMKIIα and NMDAR expression levels in the SI region. Remifentanil decreased the PWMT and PWTL at 0.5 h, 2 h, and 5 h and increased p-CaMKIIα expression in the SI region. Ketamine increased the PWMT and PWTL and reversed the p-CaMKIIα upregulation. Both BayK8644 and NMDA reversed the effect of ketamine, decreased the PWMT and PWTL, and upregulated p-CaMKIIα expression. In contrast, KN93 enhanced the effect of ketamine by reducing hyperalgesia and downregulating p-CaMKIIα expression. These results suggested that ketamine reversed RIPH by inhibiting the phosphorylation of CaMKIIα and the NMDA receptor in the SI region in mice.

Feasibility study of imaging fast neural activity in retinal tissue using Electrical Impedance Tomography.

Electrical Impedance Tomography has been recently applied to image fast neural activity in the somatosensory cerebral cortex. This non-invasive imaging modality has the unique advantage of high spatial-temporal resolution in millimeters over milliseconds. This work was designed to test an existing 32-channel EIT system, a modified UCL ScouseTom, and to discuss the feasibility of imaging neural activity in retinal tissue through computer simulation. The finite element method was used to model a retinal slice with a realistic conductivity-depth profile of the macaque eye. The conductivity perturbation was simulated in five different layers of the model. 5μVRMS white noise was added to boundary voltages. Simulation results showed that it is feasible to apply EIT in retinal tissue but the injection current is near threshold of unwanted phosphenes induction. Therefore the suggested future work are validating threshold current through animal experiments, developing electrodes with low contact impedance and mitigating noise through averaging.

Imaging fast electrical activity in the brain with electrical impedance tomography

Imaging of neuronal depolarization in the brain is a major goal in neuroscience, but no technique currently exists that could image neural activity over milliseconds throughout the whole brain. Electrical impedance tomography (EIT) is an emerging medical imaging technique which can produce tomographic images of impedance changes with non-invasive surface electrodes. We report EIT imaging of impedance changes in rat somatosensory cerebral cortex with a resolution of 2ms and <200μm during evoked potentials using epicortical arrays with 30 electrodes. Images were validated with local field potential recordings and current source-sink density analysis. Our results demonstrate that EIT can image neural activity in a volume 7×5×2mm in somatosensory cerebral cortex with reduced invasiveness, greater resolution and imaging volume than other methods. Modeling indicates similar resolutions are feasible throughout the entire brain so this technique, uniquely, has the potential to image functional connectivity of cortical and subcortical structures.

Cortical fast-spiking parvalbumin interneurons enwrapped in the perineuronal net express the metallopeptidases Adamts8, Adamts15 and Neprilysin.

The in situ hybridization Allen Mouse Brain Atlas was mined for proteases expressed in the somatosensory cerebral cortex. Among the 480 genes coding for protease/peptidases, only four were found enriched in cortical interneurons: Reln coding for reelin; Adamts8 and Adamts15 belonging to the class of metzincin proteases involved in reshaping the perineuronal net (PNN) and Mme encoding for Neprilysin, the enzyme degrading amyloid β-peptides. The pattern of expression of metalloproteases (MPs) was analyzed by single-cell reverse transcriptase multiplex PCR after patch clamp and was compared with the expression of 10 canonical interneurons markers and 12 additional genes from the Allen Atlas. Clustering of these genes by K-means algorithm displays five distinct clusters. Among these five clusters, two fast-spiking interneuron clusters expressing the calcium-binding protein Pvalb were identified, one co-expressing Pvalb with Sst (PV-Sst) and another co-expressing Pvalb with three metallopeptidases Adamts8, Adamts15 and Mme (PV-MP). By using Wisteria floribunda agglutinin, a specific marker for PNN, PV-MP interneurons were found surrounded by PNN, whereas the ones expressing Sst, PV-Sst, were not.

GluN2B N-methyl-D-aspartic acid receptor subunit mediates atorvastatin-Induced neuroprotection after focal cerebral ischemia.

Statins are potent cholesterol biosynthesis inhibitors that exert protective effects in humans and in experimental models of stroke. The mechanisms involved in these protective actions are not completely understood. This study evaluates whether atorvastatin (ATV) treatment affects the GluN1 and GluN2B subunits of the N-methyl-D-aspartic acid receptor in the somatosensory cerebral cortex at short and long periods following ischemia. Sham and ischemic male Wistar rats received 10 mg/kg of ATV or placebo by gavage every 24 hr for 3 consecutive days. The first dose was administered 6 hr after ischemia-reperfusion or the sham operation. ATV treatment resulted in faster recovery of neurological scores than placebo, prevented the appearance of pyknotic neurons, and restored microtubule-associated protein 2 and neuronal nuclei staining to control values in the somatosensory cerebral cortex and the hippocampus at 72 hr and 15 days postischemia. Furthermore, ATV prevented spatial learning and memory deficits caused by cerebral ischemia. Cerebral ischemia reduced the number of GluN1/PSD-95 and GluN2B/PSD-95 colocalization clusters in cortical pyramidal neurons and reduced the levels of brain-derived neurotrophic factor (BDNF) in the cerebral cortex. These effects of the ischemic insult were prevented by ATV, which also induced GluN2B/PSD-95 colocalization in neuronal processes and an association of GluN2B with TrkB. The GluN2B pharmacological inhibitor ifenprodil prevented the increase in BDNF levels and the motor and cognitive function recovery caused by ATV in ischemic rats. These findings indicate that GluN2B is involved in the neuroprotective mechanism elicited by ATV to promote motor and cognitive recovery after focal cerebral ischemia.

Evaluation of the clinical practicability of intraoperative optical imaging comparing three different camera setups

Intraoperative optical imaging (IOI) is a method to visualize functional activated brain areas during brain surgery using a camera system connected to a standard operating microscope. Three different high-resolution camera systems (Hamamatsu EB-CCD C7190-13W, Hamamatsu C4742-96-12G04, and Zeiss AxioCam MRm) have been evaluated for suitability to detect activated brain areas by detecting stimulation-dependent blood volume changes in the somatosensory cerebral cortex after median nerve stimulation. The image quality of the camera systems was evaluated in 14 patients with tumors around the somatosensory cortex. The intraoperative images of the brain surface were continuously recorded over 9 min. With all three camera systems, the activity maps of the median nerve area could be visualized. The image quality of a highly sensitive electron-bombarded camera was up to 10-fold lower compared with two less sensitive standard cameras. In each IOI-positive case, the activated area was in accordance with the anatomical and neurophysiological location of the corresponding cortex. The technique was found to be very sensitive, and several negative influencing factors were identified. However, all possible artifacts seem to be controllable in the majority of the cases, and the IOI method could be well adapted for routine clinical use. Nevertheless, further systematic studies are needed to demonstrate the reliability and validity of the method.

Estrogen regulation of spine density and excitatory synapses in rat prefrontal and somatosensory cerebral cortex

The steroid hormone, 17β-estradiol (E2) has been reported to enhance executive functions that are known to be mediated by the prefrontal cortex (PFC), although the underlying mechanisms remain unclear. To shed light on the potential mechanisms, we examined the effect of E2 in vivo upon spine density in the rat PFC and the somatosensory cortex (SSC), which has been implicated to be a transient storage site for information that can also contribute to working memory. The results revealed that E2 significantly enhanced the number of dendritic spines in both the SSC and PFC, as well as the expression of spinophilin. In vitro studies revealed further mechanistic insights by demonstrating that E2 enhanced AMPA GluR1 receptor expression and excitatory glutamatergic synapse formation in rat cortical neurons, without an effect upon inhibitory GABAergic synapse formation. Furthermore, E2 rapidly enhanced ERK and Akt activation in cortical neurons, and inhibitors of ERK and Akt activation significantly attenuated E2 induction of excitatory glutamatergic synapses. Administration of E2-BSA likewise significantly enhanced excitatory glutamatergic synapses in cortical neurons, and administration of an ER antagonist, ICI182,780 and a non-NMDA receptor antagonist (NBQX) significantly attenuated the effect of E2 upon enhancement of excitatory glutamatergic synapses, suggesting mediation by extranuclear estrogen receptors and involvement of non-NMDA receptor activation and signaling. As a whole, the studies demonstrate that E2 enhances spine density in both the PFC and SSC, and that E2 enhances excitatory glutamatergic synapse formation in cortical neurons via a rapid extranuclear ER-mediated signaling mechanism that involves up-regulation of GluR1 and mediation by Akt and ERK signaling pathways.

Subventricular Zone Neuroblasts Emigrate Toward Cortical Lesions

Adult subventricular zone (SVZ) neuroblasts migrate in the rostral migratory stream to the olfactory bulbs. Brain lesions generally increase SVZ neurogenesis or gliogenesis and cause SVZ cell emigration to ectopic locations. We showed previously that glia emigrate from the SVZ toward mechanical injuries of the somatosensory cerebral cortex in mice. Here we tested the hypotheses that SVZ neurogenesis increases, that neuroblasts emigrate, and that epidermal growth factor expression increases after cortical injuries. Using immunohistochemistry for phenotypic markers and BrdU, we show that newborn doublecortin-positive SVZ neuroblasts emigrated toward cerebral cortex lesions. However, the number of doublecortin-positive cells in the olfactory bulbs remained constant, suggesting that dorsal emigration was not at the expense of rostral migration. Although newborn neuroblasts emigrated, rates of SVZ neurogenesis did not increase after cortical lesions. Finally, we examined molecules that may regulate emigration and neurogenesis after cortical lesions and found that epidermal growth factor was increased in the SVZ, corpus callosum, and cerebral cortex. These results suggest that after injuries to the cerebral cortex, neuroblasts emigrate from the SVZ, that emigration does not depend either on redirection of SVZ cells or on increased neurogenesis, and that epidermal growth factor may induce SVZ emigration.

Effects of total sleep deprivation in rats with hereditary predisposition to audiogenic convulsions

In rats of the Krushinskii-Molodkina (KM) line with hereditary predisposition to audiogenic convulsions there were studied effects of total sleep deprivation for 3, 6, and 9 h by a light arousal or a slow rotation in a roller on spectral EEG characteristics in the wakefulness-sleep cycle, organization of the cycle, and intensity of convulsive symptoms at the recovery period. The data are presented on dynamics of recovery of the cycle structure for 12 h of postdeprivation period. It has been established that during and after the total sleep deprivations of any duration no paroxysmal discharges appear in EEG of hippocampus, caudate nucleus, medial central thalamic nucleus, somatosensory, visual, and auditory cerebral cortex in any of states of the wakefulness-sleep cycle. These deprivations were also shown to have no effect on the latent period value and parameters of generalized tonic-clonal audiogenic convulsions. At the same time, after 6 and 9 h of the total sleep deprivations in a slowly rotating roller there was revealed in some animals a change of the type of response to the sound stimulus. Such decrease of reaction of rats to audiogenic stimuli seems to be due to alertness of the animals. It is stated that in the KM rats, with the hidden convulsive syndrome, we failed to activate epileptiform manifestations by the used types and ways of the total sleep deprivations.

Somatosensory paths proceeding to spinal cord and brain — centripetal and centrifugal control for human movement

The flow of fast-conducting somatosensory information proceeding from the human leg, and entering sensorimotor control processes, is modulated according to the demands of limb movement. Both centripetal (proceeding in from sensory receptor discharge) and centrifugal (proceeding out from motor control centres) convergences can cause modulation, as seen in human, dog, and cat studies. Spinal H-reflexes appear to be strongly centripetally modulated in magnitude, as do initial somatosensory-evoked potentials recorded from the scalp following transmission in fast-conducting afferents from the leg. From the brain and from locomotor pattern-generators, there is also centrifugal control onto fast-conducting somatosensory pathways from the leg, both serving spinal reflexes and ascending to the brain. One expression of the centrifugal control appears to be pattern-generator modulation of cutaneous reflexes. Centrifugal control also can be seen premovement, as spinal H-reflex facilitation. Further, it can be observed as reduction of reception at somatosensory cerebral cortex, when motor learning has occurred or when stimuli are less salient for the task. Fourteen research developments have been identified that involve the generalizability of effects, specific mechanisms, and somatosensory modulation in predictive control.

Modification of GABA B1 and GABA B2 receptor subunits in the somatosensory cerebral cortex and thalamus of rats with absence seizures (GAERS)

In the present study, we have investigated GABA B receptor expression in somatosensory cortex (S1) and the ventrobasal (VB) and reticular (Rt) thalamic nuclei of Genetic Absence Epilepsy Rats from Strasbourg (GAERS), which represent an animal model for the human absence epilepsy. We focused our attention on the thalamocortical network because it has been demonstrated that absence seizures are generated in this specific circuit, which is under the control of several inhibitory, e.g. GABA, and excitatory systems. Autoradiography data obtained with the GABA B receptor antagonist [ 3 H ]CGP62349 did not show any differences in K d or B max values between control rats and GAERS. In situ hybridisation (ISH) results showed a significant increase in messenger RNA for GABA B1 in the S1 and a decrease in the VB thalamic nucleus but not in the Rt thalamic nucleus. By contrast the immunocytochemical data revealed an increased expression of both GABA B1 and GABA B2 receptor subunits in all the regions examined, somatosensory cerebral cortex, VB thalamus and Rt nucleus in GAERS compared to controls. The main finding was an up-regulation of GABA B receptor protein in the corticothalamic circuit in GAERS compared to controls.

The influence of somatosensory cortex on climbing fiber responses in the lateral hemispheres of the rat cerebellum after peripheral tactile stimulation.

This report describes the temporal relationship between the latency of responses to peripheral stimulation in primary somatosensory (SI) cerebral cortex and the timing of climbing fiber inputs to the lateral hemispheres of the rat cerebellum. Examined in the tactilely responsive regions of crus IIa in the rat, the results show that SI influences the timing of both evoked and spontaneous climbing fiber activity in these cerebellar regions without affecting the rate or probability of complex spike discharge. By reversibly blocking SI activity, we demonstrate that the absence of cortical input results in a lengthening of climbing fiber response latency to peripheral stimuli. Similarly, enhancing the cortical input by subthreshold electrical stimulation of SI results in a shortening of climbing fiber response latency. These results provide a new explanation for the tendency of the inferior olive to oscillate at 7-12 Hz and is consistent with the hypothesis that the inferior olive provides the cerebellum information about the timing of cortical computational cycles. Results are discussed in the context of previous and current hypotheses concerning the physiology and function of the inferior olive/climbing fiber system and are interpreted to provide additional evidence of a role for the cerebellum in the tactile somatosensory system.

The Influence of Somatosensory Cortex on Climbing Fiber Responses in the Lateral Hemispheres of the Rat Cerebellum after Peripheral Tactile Stimulation

This report describes the temporal relationship between the latency of responses to peripheral stimulation in primary somatosensory (SI) cerebral cortex and the timing of climbing fiber inputs to the lateral hemispheres of the rat cerebellum. Examined in the tactilely responsive regions of crus IIa in the rat, the results show that SI influences the timing of both evoked and spontaneous climbing fiber activity in these cerebellar regions without affecting the rate or probability of complex spike discharge. By reversibly blocking SI activity, we demonstrate that the absence of cortical input results in a lengthening of climbing fiber response latency to peripheral stimuli. Similarly, enhancing the cortical input by subthreshold electrical stimulation of SI results in a shortening of climbing fiber response latency. These results provide a new explanation for the tendency of the inferior olive to oscillate at 7-12 Hz and is consistent with the hypothesis that the inferior olive provides the cerebellum information about the timing of cortical computational cycles. Results are discussed in the context of previous and current hypotheses concerning the physiology and function of the inferior olive/climbing fiber system and are interpreted to provide additional evidence of a role for the cerebellum in the tactile somatosensory system.

Chronic exposure to aluminium decreases NADPH-diaphorase positive neurons in the rat cerebral cortex

Aluminium (Al) exposure is neurotoxic and is considered a possible etiological factor for many neurodegenerative disorders. Since it is known that Al impairs the glutamate–nitric oxide–cGMP pathway in neurons, this study was carried out to monitor the expression of NADPH-d in some central nervous system areas of rats after chronic administration of Al in drinking water. We tested three different nervous areas known to contain NADPH-diaphorase positive neurons: two cortical area (somatosensory cerebral cortex and cerebral cortex), a deep brain area (dorsolateral periaqueductal gray matter) and a spinal area (lumbar enlargement of the spinal cord). Our data showed that Al significantly decreased NADPH-d positive neurons in the cerebral cortex and the NADPH-d staining of many granular neurons in the cerebellum. We also found that Al did not cause neuron loss or apoptosis in the cerebral cortex. These findings suggest that the cortical nitroxidergic neurons and granule cells were a specific target of Al neurotoxicity.

Morphological characteristics and electrophysiological responses of visceral nociceptive neurons in somatosensory cerebral cortex of cat

The morphology of intracellular neurobiotin-labeled cortical neurons activated by noxious visceral stimuli in cat was reported. The electrophysiologic properties of 851 neurons and structure of 52 neurons of representative area of the greater splanchnic nerve (GSN) in the primary somatosensory cortex were described. The neurons responding to stimulation of GSN with strong intensity were referred to as viscero-nociceptive neurons (VNNs). Patterns of the responses of VNNs in SI area were excitatory, inhibitory and mixed. According to latency of discharge clusters in response, the VNNs could be classified into two kinds. The neurons only showing long latency were called specific VNNs; those having discharge clusters with both long and short latency induced by stimulus were nonspecific VNNs. Following acquisition of electrophysiological data, neurobiotin was injected into some cells by electrophoresis and their structure and location in the cerebral cortex were studied. The results provided some findings about morphological and electrophysiological characteristics of VNNs in SI area. It is thought that VNNs have more complicated morphology in the dendritic construction and axon distribution than nonvisceral nociceptive neurons (NVNNs). Most of the excitatory VNNs showed pyramidal shape and most of the inhibitory VNNs had stellate shape in camera lucida drawing. The architecture of the nonspecific VNNs might be different from specific VNNs in dendritic distribution.

Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice.

Fibroblast growth factor-2 (FGF-2) has been implicated in various signaling processes which control embryonic growth and differentiation, adult physiology and pathology. To analyze the in vivo functions of this signaling molecule, the FGF-2 gene was inactivated by homologous recombination in mouse embryonic stem cells. FGF-2-deficient mice are viable, but display cerebral cortex defects at birth. Bromodeoxyuridine pulse labeling of embryos showed that proliferation of neuronal progenitors is normal, whereas a fraction of them fail to colonize their target layers in the cerebral cortex. A corresponding reduction in parvalbumin-positive neurons is observed in adult cortical layers. Neuronal defects are not limited to the cerebral cortex, as ectopic parvalbumin-positive neurons are present in the hippocampal commissure and neuronal deficiencies are observed in the cervical spinal cord. Physiological studies showed that FGF-2-deficient adult mice are hypotensive. They respond normally to angiotensin II-induced hypertension, whereas neural regulation of blood pressure by the baroreceptor reflex is impaired. The present genetic study establishes that FGF-2 participates in controlling fates, migration and differentiation of neuronal cells, whereas it is not essential for their proliferation. The observed autonomic dysfunction in FGF-2-deficient adult mice uncovers more general roles in neural development and function.

Effects of d-AP5 and NMDA microiontophoresis on associative learning in the barrel cortex of awake rats

Experiments involving single-unit recordings and microiontophoresis were carried out in the barrel cortex of awake, adult rats subjected to whisker pairing, an associative learning paradigm where deflections of the recorded neuron's principle vibrissa (S2) are repeatedly paired with those of a non-adjacent one (S1). Whisker pairing with a 300 ms interstimulus interval was applied to 61 cells. In 23 cases, there was no other manipulation whereas in the remaining 38, pairing occurred in the presence of one of three pharmacological agents previously shown to modulate learning, receptive field plasticity and long-term potentiation: N-methyl- d-aspartic acid (NMDA) ( n=8), the NMDA receptor antagonist AP5 ( n=17) or the nitric oxide synthase inhibitor l-nitro-arginine- N-methyl-ester ( l-NAME) ( n=13). Non-associative (unpaired) experiments ( n=14) and delivery of pharmacological agents without pairing ( n=14) served as controls. Changes in neuronal responsiveness to S1 following one of these procedures were calculated and adjusted relative to changes in the responses to S2. On average, whisker pairing alone yielded a 7% increase in the responses to S1. This enhancement differed significantly from the 17% decrease obtained in the non-associative control condition and could not be attributed to variations in the state of the animals because analysis of the cervical and facial muscle electromyograms revealed that periods of increased muscular activity, reflecting heightened arousal, were infrequent (less than 4% of a complete experiment on average) and occurred randomly. The enhancement of the responses to S1 was further increased when whisker pairing was performed in the presence of l-NAME (27%) or NMDA (35%) whereas AP5 reduced it to 1%. During the delivery period, NMDA enhanced both neuronal excitability and responsiveness to S1 whereas AP5 depressed them. However, the effects of both substances disappeared immediately after administration had ended. l-NAME did not affect the level of ongoing activity and responses to S1 significantly. From these data, we concluded that, since the changes in the responses to S1 lasted longer than the periods of both whisker pairing and drug delivery, they were not residual excitatory or inhibitory drug effects on neuronal excitability. Thus, our results indicate that, relative to the unpaired controls, whisker pairing led to a 24% increase in the responsiveness of barrel cortex neurons to peripheral stimulation and that these changes were modulated by the local application of pharmacological agents that act upon NMDA receptors and pathways involving nitric oxide. We can infer that somatosensory cerebral cortex is one site where plasticity emerges following whisker pairing.