Sharp, local synchrony among putative feed-forward inhibitory interneurons of rabbit somatosensory cortex

Many suspected inhibitory interneurons (SINs) of primary somatosensory cortex (S1) receive a potent monosynaptic thalamic input (thalamocortical SINs, SINstc). It has been proposed that nearly all such SINstc of a S1 barrel column (BC) receive excitatory synaptic input from each member of a subpopulation of neurons within the topographically aligned ventrobasal (VB) thalamic barreloid. Such a divergent and convergent network leads to several testable predictions: sharply synchronous activity should occur between SINstc of a BC, sharp synchrony should not occur between SINstc of neighboring BCs, and sharp synchrony should not occur between SINs or other neurons of the same BC that do not receive potent monosynaptic thalamic input. These predictions were tested by cross-correlating the activity of SINstc of the same and neighboring BCs. Correlations among descending corticofugal neurons of layer 5 (CF-5 neurons, identified by antidromic activation) and other neurons that receive little or no monosynaptic VB input also were examined. SINs were identified by a high-frequency (>600 Hz) burst of three or more spikes elicited by VB stimulation and had action potentials of short duration. SINstc were further differentiated by short synaptic latencies to electrical stimulation of VB thalamus (<1.7 ms) and to peripheral stimulation (<7.5 ms). The above predictions were confirmed fully. 1) Sharp synchrony (+/-1 ms) was seen between all SINstc recorded within the same BC (a mean of 4.26% of the spikes of each SINtc were synchronized sharply with the spikes of the paired SINtc). Sharp synchrony was not dependent on peripheral stimulation, was not oscillatory, and survived general anesthesia. Sharp synchrony was superimposed on a broader synchrony, with a time course of tens of milliseconds. 2) Little or no sharp synchrony was seen when CF-5 neurons were paired with SINstc or other neurons of the same BC. 3) Little or no sharp synchrony was seen when SINstc were paired with other SINstc located in neighboring BCs. Intracellular recordings obtained from three SINs in the fully awake state supported the assertion that SINs are GABAergic interneurons. Each of these cells met our extracellular criteria for identification as a SIN, each had a spike of short duration (0.4-0.5 ms), and each responded to a depolarizing current pulse with a nonadapting train of action potentials. These results support the proposed network linking VB barreloid neurons with SINstc within the topographically aligned BC. We suggest that sharp synchrony among SINstc results in highly synchronous inhibitory postsynpatic potentials (IPSPs)in the target neurons of these cells and that these summated IPSPs may be especially effective when excitatory drive to target cells is weak and asynchronous.     

Physiological properties of inhibitory interneurons in cat striate cortex

The current knowledge of the catecholaminergic innervation of the mammalian adrenal cortex is summarized, and macro- and microscopic neuromorphology, including the central nervous system connections of the adrenal cortex, is briefly discussed. Morphological and functional data on the catecholaminergic (i.e., noradrenergic) innervation of the adrenal cortex are reviewed. Experimental data suggest that in addition to the regulation of adrenal blood flow, the noradrenergic innervation has a primary influence on zona glomerulosa cells possibly via beta 1 adrenergic and dopaminergic receptors (DA2 subtype via inhibiting T-type Ca2+ channels) It is concluded that the local, modulatory effect of noradrenergic nerve fibres, terminating in the close vicinity of the zona glomerulosa cells, on the systemic renin-angiotensin-aldosterone and other peptide cascade may be influenced by neuropeptides, particularly neuropeptide Y and vasoactive intestinal peptide.     

Neuronal correlates of auditory induction in the cat cortex

Cells in the cat primary auditory cortex (A1) were investigated to see whether they could integrate sound signals over time. A1 cells responded well to frequency-modulated sweeps. When a portion of the sweep was replaced by silence the response was weakened considerably. However, the response strength was restored when the silent portion was replaced by a burst of band noise, even though the cells did not respond to the burst of noise alone. These results indicate that A1 cells do not respond simply to instantaneous characteristics of acoustic stimuli but respond to those integrated over time.     

Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain

How neuronal activity changes cerebral blood flow is of biological and practical importance. The rodent whisker-barrel system has special merits as a model for studies of changes in local cerebral blood flow (LCBF). Stimulus-evoked changes in neural firing and 'intrinsic signals' recorded through a cranial window were used to define regions of interest for repeated flow measurements. Whisker-activated changes in flow were measured with intravascular markers at the pia. LCBF changes were always prompt and localized over the appropriate barrel. Stimulus-related changes in parenchymal flow monitored continuously with H2 electrodes recorded short latency flow changes initiated in middle cortical layers. Activation that increased flow to particular barrels often led to reduced flow to adjacent cortex. Dye was injected into single penetrating arterioles from the pia of the fixed brain and injected into arterioles in slices of cortex where barrels were evident without stains. Arteriolar and venular domains at the surface were not directly related to underlying barrels. Capillary tufts in layer IV were mainly coincident with barrels. The matching between a capillary plexus (a vascular module) and a barrel (a functional neuronal unit) is a spatial organization of neurons and blood vessels that optimizes local interactions between the two. The paths of communication probably include: neurons to neurons, neurons to glia, neurons to vessels, glia to vessels, vessels to vessels and vessels to brain. Matching a functional grouping of neurons with a vascular module is an elegant means of reducing the risk of embarrassment for energy-expensive neuronal activity (ion pumping) while minimizing energy spent for delivery of the energy (cardiac output). For imaging studies this organization sets biological limits to spatial, temporal and magnitude resolution. Reduced flow to nearby inactive cortex enhances local differences.     

Involvement of protein kinase C during activation of the mitogen-activated protein kinase cascade by leukemia inhibitory factor. Evidence for participation of multiple signaling pathways

We show here that treatment of 3T3-L1 cells with leukemia inhibitory factor (LIF) stimulates the activation of mitogen-activated protein kinase kinase (MAPKK), mitogen-activated protein kinase (MAPK), and S6 protein kinase (S6K) activities both in a time- and dose-dependent manner. A single peak of MAPKK activity, four peaks of activity against the S6 synthetic peptide, RRLSSLRA (S6 peptide), and three distinct peaks toward myelin basic protein (MBP) were observed after Mono-Q chromatography of LIF-stimulated cell extracts. Two of the MBP kinase activities correlated with the stimulation of extracellular signal-regulated kinases 1 and 2. Interestingly, down-regulation of protein kinase C (PKC) by chronic treatment of 3T3-L1 cells with phorbol ester was found to attenuate, but not block, the LIF-mediated stimulation of MAPKK, MAPK, and S6K activities in 3T3-L1 cells. Treatment of 3T3-L1 cells with epidermal growth factor increased MAPKK, MAPK, and S6K activities to a similar extent as LIF, but this activation was not attenuated by down-regulation of PKC. Our results suggest that the full activation of the MAPK cascade by LIF may require inputs from multiple signaling pathways, one of which is dependent upon the presence of functional PKC.     

Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord

Inductive factors are known to direct the regional differentiation of the vertebrate central nervous system (CNS) but their role in the specification of individual neuronal cell types is less clear. We have examined the function of GDF7, a BMP family member expressed selectively by roof plate cells, in the generation of neuronal cell types in the dorsal spinal cord. We find that GDF7 can promote the differentiation in vitro of two dorsal sensory interneuron classes, D1A and D1B neurons. In Gdf7-null mutant embryos, the generation of D1A neurons is eliminated but D1B neurons and other identified dorsal interneurons are unaffected. These findings show that GDF7 is an inductive signal from the roof plate required for the specification of neuronal identity in the dorsal spinal cord and that GDF7 and other BMP family members expressed by the roof plate have non-redundant functions in vivo. More generally, these results suggest that BMP signaling may have a prominent role in the assignment of neuronal identity within the mammalian CNS.     

Solution for Flow Rates across the Wellbore in a Two-Zone Confined Aquifer

A closed-form solution for transient flow rates across the wellbore in a confined aquifer is derived from a two-zone radial ground-water flow equation subject to the boundary condition of keeping a constant head at the well radius. An aquifer may be considered as a two-zone system if the formation properties near the wellbore are significantly changed due to the well construction and/or well development. An efficient numerical approach is used to evaluate this newly derived solution. Values of the transient flow rate are provided in a tabular form and compared with those obtained by numerical inversion for the Laplace-domain solution. The results show that the two solutions are in good agreement. This newly derived solution can be used not only for predicting the transient flow rate across the wellbore but also for identifying the effects of a skin with a finite thickness on the estimation of transient flow rates in a ground-water system with two different formation properties.     

Evidence that trigeminal brainstem interneurons form subpopulations to produce different forms of mastication in the rabbit

To determine how trigeminal brainstem interneurons pattern different forms of rhythmical jaw movements, four types of motor patterns were induced by electrical stimulation within the cortical masticatory areas of rabbits. After these were recorded, animals were paralyzed and fictive motor output was recorded with an extracellular microelectrode in the trigeminal motor nucleus. A second electrode was used to record from interneurons within the lateral part of the parvocellular reticular formation (Rpc-alpha, n = 28) and gamma- subnucleus of the oral nucleus of the spinal trigeminal tract (NVspo-gamma, n = 68). Both of these areas contain many interneurons projecting to the trigeminal motor nucleus. The basic characteristics of the four movement types evoked before paralysis were similar to those seen after the neuromuscular blockade, although cycle duration was significantly decreased for all patterns. Interneurons showed three types of firing pattern: 54% were inactive, 42% were rhythmically active, and 4% had a tonic firing pattern. Neurons within the first two categories were intermingled in Rpc-alpha and NVspo-gamma: 48% of rhythmic neurons were active during one movement type, 35% were active during two, and 13% were active during three or four patterns. Most units fired during either the middle of the masseter burst or interburst phases during fictive movements evoked from the left caudal cortex. In contrast, there were no tendencies toward a preferred coupling of interneuron activity to any particular phase of the cycle during stimulation of other cortical sites. It was concluded that the premotoneurons that form the final commands to trigeminal motoneurons are organized into subpopulations according to movement pattern.     

Increased striatal proenkephalin mRNA subsequent to production of spreading depression in rat cerebral cortex: activation of corticostriatal pathways?

Cortical Spreading Depression (CSD) is a slowly propagating wave of depolarization and negative interstitial DC potential, that when induced in the rat brain extends across the entire homolateral hemisphere. Despite evidence that CSD does not penetrate into subcortical regions, neurochemical changes in areas anatomically connected to cortex have been reported. In this study in situ hybridization histochemistry was used to examine the levels of cholecystokinin (CCK), proenkephalin (ENK) and prodynorphin (DYN) mRNA in cortex and forebrain basal ganglia following KCl-induced CSD. Unilateral CSD was induced by topical application of 3 M KCl ( approximately 10 microliter) onto the right parietal cortex for 10 min and rats were then killed 1-6 h and 1-28 days later. CCK mRNA levels were increased (P<0.01) in the ipsilateral neocortex 3 h after CSD (13% above levels in contralateral side), reached a peak at 2 days ( approximately 70%) and were still elevated at 7 (30%) but not, 14 or 28 days later. Unilateral CSD also produced a rapid and sustained increase (P<0.05) in ENK mRNA in ipsilateral piriform cortex (from 3 h to 2 days; 70-250% above contralateral), and a delayed increase in caudate putamen and olfactory tubercle at 1 and 2 days ( approximately 25% in both regions), but levels were again equivalent to control at 7 days and beyond. In contrast, no marked changes in neocortical ENK mRNA, or DYN mRNA in both cortex and basal ganglia, were observed under these conditions. These findings demonstrate that CSD has specific, rapid and long-lasting effects on neuropeptide expression in neocortex and subcortical areas. CSD-induced changes in mesostriatal ENK mRNA are proposed to reflect synaptic activation of local neurons via cortical afferent projections.     

Neuronal generators of visual evoked potentials in humans: visual processing in the human cortex

PURPOSE: We wished to define the localization of cortical generators of visual (pattern) evoked potentials (VEP) and the temporal sequence of activation in the occipital region. METHODS: In 4 candidates for epilepsy surgery, a large array of subdural electrodes was placed over occipital areas. Checkerboard pattern reversal stimuli were generated and the epileptogenic focus was localized and functionally mapped. Magnetic resonance imaging did not show any occipital lesions in any of the 4 patients. RESULTS: The area first activated was the lingual gyrus in the mesial occipital lobe (negative potential peaks at approximately 70 ms), followed by an area superior to the calcarine fissure (negative peaks at approximately 80 ms). Later (starting at approximately 90 ms), there were positive potentials over the occipital pole and lingual gyrus, followed by potentials at the lateral occipital lobe. CONCLUSIONS: These data support the idea that VEP are generated in the mesial and lateral occipital cortex by different circumscribed neuronal generators with different latencies of activation. The scalp-recorded N1 and P1 potential peaks most likely derive from the progressive activation of neuronal masses in different regions of the occipital lobe.     

Precocious development of parvalbumin-like immunoreactive interneurons in the hippocampal formation and entorhinal cortex of the fetal cynomolgus monkey

The calcium-binding protein parvalbumin (PV), a reliable marker of the hippocampal basket and chandelier cells, is first expressed on embryonic day 83 (E83), corresponding to midgestation of the macaque monkey, in restricted hippocampal groups of immature neurons (Berger and Alvarez [1996] J. Comp. Neurol. 366:674-699). In the present study, PV-like immunoreactivity (LIR) was used to follow the further development of this subclass of interneurons. Asynchronous area-specific developmental sequences were observed, predominating initially in the caudal half of the hippocampal formation and the laterocaudal division of the entorhinal cortex and occurring relatively simultaneously in the interconnected hippocampal and entorhinal subfields. Dendritic elongation of PV-like immunoreactive interneurons and perisomatic distribution of PV-like immunoreactive terminal boutons on their cellular targets were first observed in the subiculum around E127; then from E127 to E142 in CA3/CA2 and layers III-V of the entorhinal cortex and, to a lesser extent in CA1, the dentate hilus and deep granule cell layer; and finally from E156 to postnatal day 12 in the rest of the dentate gyrus, the presubiculum and parasubiculum, and layers III-II-I of the entorhinal cortex. These data provide the first indication that a population of basket cells, a major gamma-aminobutyric acid (GABA)ergic component of the hippocampal intrinsic inhibitory circuitry, reaches its cellular targets several weeks before birth in primates in contrast to rodents. The role of the prenatal PV expression in the hippocampal formation of nonhuman primates and whether it coincides with the onset of postsynaptic inhibitory potentials or is accompanied or preceded by a period of gamma-aminobutyric acid-mediated excitatory effects as in rat pups, are crucial questions. They underline the need to pursue direct investigations on primates to be able to legitimately extrapolate the data obtained in rodents.     

Generalized Analytical Solutions for Groundwater Head in a Horizontal Aquifer in the Presence of Subsurface Drains

Generalized analytical solutions for groundwater head in horizontal aquifers in the presence of parallel subsurface drains are obtained considering a transient rate of recharge as a power series (polynomial) function and depth-dependent rate of evapotranspiration. A function, new to analytical drainage studies, is proposed for correctly representing the depth-dependent rate of evapotranspiration. The solutions are obtained considering the practical situation of drains placed at a shallow depth in a considerable depth of aquifer. Two conditions of large and small saturated thicknesses in comparison to the changes in groundwater head are considered. A mathematical criterion is proposed to distinguish between large and small saturated thicknesses.     

Neuronal correlates of amblyopia in the visual cortex of macaque monkeys with experimental strabismus and anisometropia

Amblyopia is a developmental disorder of pattern vision. After surgical creation of esotropic strabismus in the first weeks of life or after wearing -10 diopter contact lenses in one eye to simulate anisometropia during the first months of life, macaques often develop amblyopia. We studied the response properties of visual cortex neurons in six amblyopic macaques; three monkeys were anisometropic, and three were strabismic. In all monkeys, cortical binocularity was reduced. In anisometropes, the amblyopic eye influenced a relatively small proportion of cortical neurons; in strabismics, the influence of the two eyes was more nearly equal. The severity of amblyopia was related to the relative strength of the input of the amblyopic eye to the cortex only for the more seriously affected amblyopes. Measurements of the spatial frequency tuning and contrast sensitivity of cortical neurons showed few differences between the eyes for the three less severe amblyopes (two strabismic and one anisometropic). In the three more severely affected animals (one strabismic and two anisometropic), the optimal spatial frequency and spatial resolution of cortical neurons driven by the amblyopic eye were substantially and significantly lower than for neurons driven by the nonamblyopic eye. There were no reliable differences in neuronal contrast sensitivity between the eyes. A sample of neurons recorded from cortex representing the peripheral visual field showed no interocular differences, suggesting that the effects of amblyopia were more pronounced in portions of the cortex subserving foveal vision. Qualitatively, abnormalities in both the eye dominance and spatial properties of visual cortex neurons were related on a case-by-case basis to the depth of amblyopia. Quantitative analysis suggests, however, that these abnormalities alone do not explain the full range of visual deficits in amblyopia. Studies of extrastriate cortical areas may uncover further abnormalities that explain these deficits.     

Neuronal encoding of conditional stimulus duration in the cingulate cortex and the limbic thalamus of rabbits.

Neuronal activity in cingulate cortex was recorded during discriminative active avoidance conditioning of rabbits. In one subpopulation of neurons, brief (200 and 500 msec) conditional stimuli (CSs) elicited greater average cingulate cortical training-induced neuronal discharges during conditioned response (CR) acquisition than did a long (5,000 msec) CS, and the amount of neuronal discrimination between CS+ and CS– was greater in response to the brief CSs than to the long CS. Neurons in a different subpopulation did not encode CS duration per se but were sensitive to the novelty of the CS duration. Medial dorsal and anteroventral thalamic neurons were suppressed by novel CS durations that activated novelty-sensitive neurons in related cingulate cortical areas. These results are discussed in relation to a theoretical model of the neural mediation of avoidance conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distribution of inhibitory synapses on the somata of pyramidal neurons in cat motor cortex

The mechanisms by which cortical neurons perform spatial and temporal integration of synaptic inputs are dependent, in large part, on the numbers, types, and distributions of their synapses. To further our understanding of these integrative mechanisms, we examined the distribution of synapses on identified classes of cortical neurons. Pyramidal cells in the cat motor cortex projecting either to the ipsilateral somatosensory cortex or to the spinal cord were labeled by the retrograde transport of horseradish peroxidase. Entire soma of selected corticocortical and corticospinal cells were examined using serial-section electron microscopy. The profiles of these somata and the synapses formed with each of these profiles were reconstructed from each thin section with a computer-aided morphometry system. All somatic synapses were of the symmetrical, presumably inhibitory type. For both cell types, these synapses were not homogeneously distributed over the somatic membrane, but were clustered at several discrete zones. The number and density of synapses on the somata of different corticocortical and corticospinal neurons were not significantly different. However, the density of these synapses was inversely correlated with the size of their postsynaptic somata. We discuss the significance of these findings to the integrative properties of cortical neurons.     

Axon projections of reciprocal inhibitory interneurons in the spinal cord of young Xenopus tadpoles and implications for the pattern of inhibition during swimming and struggling

We have examined the morphology and longitudinal axon projections of a population of spinal commissural interneurons in young Xenopus tadpoles. We aimed to define how the distribution of axons of the whole population constrains the longitudinal distribution of the inhibition they mediate. Forty-three neurons at different positions were filled intracellularly with biocytin and processed with avidin-conjugated horseradish peroxidase. Soma size did not vary longitudinally and only one ipsilateral axon was found. Contralateral axons ascended, descended, or usually branched to do both. Total axon length and the extent of dendritic arborisation decreased caudally. The distributions of ascending and descending axon lengths were different; there were more long ascending (mean 737 +/- standard deviation 365 microm) than long descending (447 +/- 431 microm) axons. We used the axon length distribution data with existing data on the distribution of commissural interneuron somata to calculate the overall longitudinal density of these inhibitory axons. Axon numbers showed a clear rostrocaudal gradient. Axon length distributions were then incorporated into a simple spatiotemporal model of the forms of inhibition during swimming and struggling motor patterns. The model predicts that the peak of inhibition on each cycle will decrease from head to tail in both motor patterns, a feature already confirmed physiologically for swimming. It also supports a previous proposal that ascending inhibition during struggling shortens cycle period by shortening rostral motor bursts, whereas descending inhibition could delay subsequent burst onset.