Altered spatial patterns of functional thalamocortical connections in the barrel cortex after neonatal infraorbital nerve cut revealed by optical recording.

In rodents, the somatosensory cortex has a cell aggregation cluster termed the barrel, reflecting a whisker vibrissa, and this barrel formation is disrupted by infraorbital nerve cut at birth. In the present study, we prepared thalamocortical slice preparations from rats that received infraorbital nerve cut either at birth or at postnatal day (P) 7 and those from normal rats, recorded the optical response reflecting neural excitation in the somatosensory cortex with a voltage-sensitive dye (RH482) and compared the optical responses from lesioned rats with those from normal rats. In normal rats at P10, the optical response elicited electrically by thalamic stimulation propagated to the cortex, and then several patchy clusters appeared in layer IV. The size and location of these patchy responses precisely matched either barrels identified by cytochrome oxidase staining or terminal arbors of thalamocortial axons stained with biotinylated dextran amine. In contrast, at P10 in P0-lesioned rats, clusters having a wider horizontal width but smaller amplitude than those seen in normal rats appeared in layer IV. Correspondingly, neither cytochrome oxidase staining nor biotinylated dextran amine labeling of thalamocortical axons showed any barrel-like clusters or glomerular axon terminals. Likewise, at P5-P6, the tangential width of clusters in layer IV were larger than that in normal rats. At P10 in P7-lesioned rats, small cluster-matched barrels were seen in the optical response as well as in normal rats. These results suggest that P0 infraorbital nerve cut interrupted segregation of functional synapses into the barrels and retarded the maturation of thalamocortical transmission.

Protein and RNA synthesis-dependent and -independent LTPs in developing rat visual cortex.

Multiple forms of synaptic potentiation have been described, but their involvement in development versus learning is unknown. To address this, we examined whether long-term potentiation (LTP) in visual cortex requires protein or RNA synthesis using slice preparations. Theta-burst stimulation of white matter induced two distinct types of LTP in layer 4. A slowly developing LTP, preferentially induced in juveniles, was blocked by protein and RNA synthesis inhibitors and was L-type calcium channel dependent. A quickly developing LTP, induced in juveniles and adults, was independent of macromolecular synthesis and required N-methyl-D-aspartate receptor activation. Thus, slow LTP might account for developmental plasticity in visual cortex including the activity-dependent refinement of neural circuitry while fast LTP might underlie the changes in synaptic strength that may participate in visual learning and memory.

Roles of GABAergic inhibition and NMDA receptor subunits in the spatio-temporal integration in the cerebellar cortex of mice.

The cerebellar cortex consists of relatively small numbers of identified neuronal types, which form simple and well-defined layers. However, a direct high-resolution demonstration of spatio-temporal pattern of information transmission there has been lacking. Using an optical recording technique with a membrane-potential sensitive dye, we studied the spatio-temporal pattern of excitation propagation induced by white matter stimulation in the slice preparations. We focused on physiological roles of inhibitory synapses and N-methyl-D-aspartate (NMDA) receptors. White matter stimulation induced postsynaptic long-lasting depolarization in the granular layer and transient depolarization in the molecular layer, respectively. Inhibitory synapses modestly suppressed the amplitude of slow depolarization in the granular layer, whereas they exerted powerful lateral inhibition in the molecular layer. Using mutant mice deficient in NMDA receptor subunits NR2A and/or NR2C, we also demonstrated that the NR2A and NR2C subunits expressed in granule neurons contribute to the early and late components of slow depolarization respectively, and that both subunits cooperatively support the temporal summation of depolarization. Taking into account the anatomical organization of the cerebellar cortex, these results might suggest that the granular layer is specialized more in the temporal integration of input signals and the molecular layer in the spatial integration.

Juxtacellular labeling of tonically active neurons and phasically active neurons in the rat striatum.

Tonically active neurons (TANs) and phasically active neurons (PANs) are widely believed to be the cholinergic interneurons and GABAergic projection neurons, respectively, in the striatum based on in vivo intracellular recordings coupled with morphological examinations of anesthetized rats, and on histochemical, electrophysiological, and labeling studies of in vitro slice preparations. TANs of alert behaving animals exhibit prolonged pause responses to behaviorally significant events. PANs, on the other hand, are mostly inactive when subjects are quiet and not performing any actions, but exhibit burst discharges in response to external stimuli and/or voluntary actions. Several other types of interneurons have also been identified in the striatum, such as parvalbumin-containing GABAergic interneurons (fast-spiking cells), somatostatin-containing interneurons, and calretinin-containing interneurons. To identify the neurochemical and morphological characteristics of TANs and PANs in a more direct manner, we conducted juxtacellular labeling, combining electrophysiology with immunohistochemistry and morphology in anesthetized rats. All of the juxtacellularly labeled TANs (n=3) among those recorded (n=10) were ChAT-positive and had large cell somata with aspiny dendrites. Thus, although our observations are based on a limited number of neurons, our findings provide the most convincing evidence to date that TANs in the striatum are cholinergic neurons. We also found that the majority of PANs are GABA-immunoreactive (46 of 48 tested) and approximately two-thirds had spiny dendrites (30 of 48 tested), indicating that the majority are medium-sized, spiny, GABAergic projection neurons, consistent with general beliefs. Conversely, the remaining one-third of PANs had aspiny dendrites (n=18), indicating that they were interneurons. Therefore, the present study reveals that TANs are cholinergic neurons and that the majority of PANs are medium-sized, spiny, GABAergic projection neurons, while a smaller number are GABAergic interneurons.

Impact of space-energy correlation on variable range hopping in a transistor.

Hopping conduction in transistors, i.e., under a transverse electric field, is addressed using percolation theory with a space-energy correlation in the density of states of the impurity band. The computation of the percolation threshold over an extended range of correlation parameters enables us to derive a formula, which, while giving the classical results in the low field limit, describes the emergence of a specific variable range hopping in the high field case. An application of this formula to experimentally extract the localization radius is also proposed.

Neuronal responsiveness to three-dimensional motion in cat posteromedial lateral suprasylvian cortex.

The neuronal responsiveness to three-dimensional (3D) motion in cat posteromedial lateral suprasylvian (PMLS) cortex was studied using a computer-controlled, stereoscopic 3D graphic display capable of reproducing the major visual cues for natural 3D motion, including motion disparity, size, texture, and shading changes. The animals were anesthetized with nitrous oxide supplemented with alphaxalone, and paralysis prevented eye movement. Systematic investigation of neuronal responsiveness to 3D motions in 26 different directions revealed that more than half of the PMLS cells were selectively responsive to approaching (AP cells, 112 of 271) or recessive motion (RC cells, 64 of 271). The remaining cells were selectively responsive to frontoparallel motion (FP cells, 49 of 271) or nonselectively responsive to motion in multiple directions (NS cells, 46 of 271). The dependency on these visual cues was investigated as a reduction in the response amplitude or the response selectivity for the removal of a single cue from the motion stimuli containing the full visual cues. The AP and RC cells showed a strong dependency on the motion disparity cue, moderate dependency on the size cue, and weak dependency on the texture and shading cues. The FP cells showed no dependency on those visual cues. The cue dependency analysis indicated the existence of nonlinear interactions between those visual cues. Comparison of the responses to a combination of the motion disparity and size cues with the summed responses to each of the individual cues revealed that the responses to the combined cues are roughly predicted as a linear sum between the preferred responses. This comparison also showed nonlinear summation between the nonpreferred responses, i.e., responses to the combined cues were smaller than the summed responses. A similar quasilinear summation of the preferred responses between the two eyes and a nonlinear summation of the nonpreferred responses were found in the AP and RC cells for the motion disparity stimulus. All of these observations indicate that quasilinear and nonlinear interactions of the responses to various stimulus elements underlie the 3D motion responsiveness of the PMLS cells.

Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination.

The role of inhibitory Golgi cells in cerebellar function was investigated by selectively ablating Golgi cells expressing human interleukin-2 receptor alpha subunit in transgenic mice, using the immunotoxin-mediated cell targeting technique. Golgi cell disruption caused severe acute motor disorders. These mice showed gradual recovery but retained a continuing inability to perform compound movements. Optical and electrical recordings combined with immunocytological analysis indicated that elimination of Golgi cells not only reduces GABA-mediated inhibition but also attenuates functional NMDA receptors in granule cells. These results demonstrate that synaptic integration involving both GABA inhibition and NMDA receptor activation is essential for compound motor coordination. Furthermore, this integration can adapt after Golgi cell elimination so as not to evoke overexcitation by the reduction of NMDA receptors.