Slices Of Rat Visual Cortex Research Articles

Phenylglycine analogs are inhibitors of the neutral amino acid transporters ASCT1 and ASCT2 and enhance NMDA receptor-mediated LTP in rat visual cortex slices

The N-methyl-d-aspartate receptor (NMDA) co-agonist d-serine is a substrate for the neutral amino acid transporters ASCT1 (SLC1A4) and ASCT2 (SLC1A5). We identified l-phenylglycine (PG) and its analogs as inhibitors of ASCT1 and ASCT2. PG analogs were shown to be non-substrate inhibitors of ASCT1 and ASCT2 with a range of activities relative to other amino acid transport systems, including sodium-dependent glutamate transporters, the sodium-independent d-serine transporter asc-1 and system L. L-4-chloroPG was the most potent and selective ASCT1/2 inhibitor identified. The PG analogs facilitated theta-burst induced long-term potentiation in rat visual cortex slices in a manner that was dependent on extracellular d-serine. For structurally-related PG analogs, there was an excellent correlation between ASCT1/2 transport inhibition and enhancement of LTP which was not the case for inhibition of asc-1 or system L. The ability of PG analogs to enhance LTP is likely due to inhibition of d-serine transport by ASCT1/2, leading to elevated extracellular levels of d-serine and increased NMDA receptor activity. These results suggest that ASCT1/2 may play an important role in regulating extracellular d-serine and NMDA receptor-mediated physiological effects and that ASCT1/2 inhibitors have the potential for therapeutic benefit.

Postnatal Development of Intrinsic and Synaptic Properties Transforms Signaling in the Layer 5 Excitatory Neural Network of the Visual Cortex

Information flow in neocortical circuits is regulated by two key parameters: intrinsic neuronal properties and the short-term activity-dependent plasticity of synaptic transmission. Using multineuronal whole-cell voltage recordings, we characterized the postnatal maturation of the electrophysiological properties and short-term plasticity of excitatory synaptic transmission between pairs of layer 5 (L5) pyramidal neurons (n = 158) in acute slices of rat visual cortex over the first postnatal month. We found that the intrinsic and synaptic properties of L5 pyramidal neurons develop in parallel. Before postnatal day 15 (P15), intrinsic electrophysiological properties were tuned to low-frequency operation, characterized by high apparent input resistance, a long membrane time constant, and prolonged somatic action potentials. Unitary excitatory synaptic potentials were of large amplitude (P11-P15; median, 514 μV), but showed pronounced use-dependent depression during prolonged regular and physiologically relevant presynaptic action potential firing patterns. In contrast, in mature animals we observed a developmental decline of the peak amplitude of unitary EPSPs (P25-P29; median, 175 μV) paralleled by a decrease in apparent input resistance, membrane time constant, and somatic action potential duration. Notably, synaptic signaling of complex action potential firing patterns was also transformed, with P25-P29 connections faithfully signaling action potential trains at frequencies up to 40 Hz (1st to 50th action potential ratio, 0.91 ± 0.12). Postnatal refinement of intrinsic properties and short-term plasticity therefore transforms the capacity of the L5 excitatory neural network of the visual cortex to generate and process patterns of action potential firing and contribute to network activity.

High‐frequency gamma oscillations coexist with low‐frequency gamma oscillations in the rat visual cortex in vitro

Synchronization of neuronal activity in the visual cortex at low (30-70 Hz) and high gamma band frequencies (> 70 Hz) has been associated with distinct visual processes, but mechanisms underlying high-frequency gamma oscillations remain unknown. In rat visual cortex slices, kainate and carbachol induce high-frequency gamma oscillations (fast-gamma; peak frequency approximately 80 Hz at 37 degrees C) that can coexist with low-frequency gamma oscillations (slow-gamma; peak frequency approximately 50 Hz at 37 degrees C) in the same column. Current-source density analysis showed that fast-gamma was associated with rhythmic current sink-source sequences in layer III and slow-gamma with rhythmic current sink-source sequences in layer V. Fast-gamma and slow-gamma were not phase-locked. Slow-gamma power fluctuations were unrelated to fast-gamma power fluctuations, but were modulated by the phase of theta (3-8 Hz) oscillations generated in the deep layers. Fast-gamma was spatially less coherent than slow-gamma. Fast-gamma and slow-gamma were dependent on gamma-aminobutyric acid (GABA)(A) receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and gap-junctions, their frequencies were reduced by thiopental and were weakly dependent on cycle amplitude. Fast-gamma and slow-gamma power were differentially modulated by thiopental and adenosine A(1) receptor blockade, and their frequencies were differentially modulated by N-methyl-D-aspartate (NMDA) receptors, GluK1 subunit-containing receptors and persistent sodium currents. Our data indicate that fast-gamma and slow-gamma both depend on and are paced by recurrent inhibition, but have distinct pharmacological modulation profiles. The independent co-existence of fast-gamma and slow-gamma allows parallel processing of distinct aspects of vision and visual perception. The visual cortex slice provides a novel in vitro model to study cortical high-frequency gamma oscillations.

Correlations and Synchrony in threshold neuron models

Event Abstract Back to Event Correlations and Synchrony in threshold neuron models Tatjana Tchumatchenko1*, Aleksey Malyshe2, Theo Geisel1, Maxim Volgushev3, 4 and Fred Wolf1 1 BCCN Göttingen and Max Planck Institute for Dynamics and Self-Organization, Germany 2 Inst. of Higher Nervous Activity and Neurophysiology, RAS, Russia 3 Ruhr-University, Dep. of Neurophysiology, Germany 4 University of Connecticut, United States Experimental studies reveal significant temporal and interneuronal correlations of subthreshold Membrane Potential (MP) fluctuations of cortical neurons in vivo. How temporal input correlations are transferred to interneuronal spike correlations is largely unknown and inferring the underlying input correlations from observed spike correlations is a challenge. To understand this relation, we used a simple analytical framework for the analysis of spike correlations between neurons driven by correlated inputs [1] to examine the quantitative determinants of the synchronization strength and acuity of a pair of neurons subject to a variable percentage of common fluctuating input of different correlation times. We calculated the autoconditional firing rate of an individual neuron and analyzed its short and long time asymptotics. In the limit of small times, we find an algebraic rise out of period of intrinsic silence after each spike that reflects the temporal correlations of the inputs and is independent of refractory properties of the AP generator. For large time lags, we find a substantial influence of the second derivative of the voltage correlation function. Furthermore, we evaluated the cross conditional firing rate of a pair of neurons for low and high common input fraction and with firing rate heterogeneity. In the low correlation regime, we identified a rate dependence of the rate of synchronous firing corroborating previous observations [2]. In the high correlation regime, however, the synchronous rate ceases to depend on the stationary firing rate and voltage correlation function of individual neurons. For all strengths of correlations the model predicts the appearance of a systematic delay of firing of the lower rate neuron relative to the higher rate neuron. To test these theoretical predictions, we performed in vitro experiments in slices of rat visual cortex and injected in pyramidal neurons fluctuating currents with a varying degree of common input. Cross and autoconditional firing rates computed from these recordings, confirmed all basic theoretical predictions of our formalism.

Homer 1a Suppresses Neocortex Long-Term Depression in a Cortical Layer-Specific Manner

Homer1a/Vesl-1S is an activity-dependently induced member of the scaffold protein family Homer/Vesl, which is known to link group I metabotropic glutamate receptors (mGluRs) to endoplasmic calcium release channels and to regulate them. Here we studied roles of Homer 1a in inducing long-term depression (LTD) in rat visual cortex slices. Homer 1a protein was injected by diffusion from whole cell patch pipettes. In layer VI pyramidal cells, LTD was reduced in magnitude with Homer 1a. LTD in layer VI was suppressed by applying antagonists of mGluR5, a subtype of group I mGluRs expressed with higher density than mGluR1 in neocortex pyramidal cells, or inositol-1,4,5-triphosphate receptors (IP3Rs) but not that against N-methyl-d-aspartate receptors (NMDARs). In layer II/III or layer V, Homer 1a injection was unable to affect LTD, which is mostly dependent on NMDARs and not on group I mGluRs in these layers. To examine the effects of endogenous Homer 1a, electroconvulsive shock (ECS) was applied. Homer 1a thereby induced, as did Homer 1a injection, reduced LTD magnitude in layer VI pyramidal cells and failed to do so in layer II/III or layer V pyramidal cells. These results indicate that both exo- and endogenous Homer 1a suppressed LTD in a cortical layer-specific manner, and its layer-specificity may be explained by the high affinity of Homer 1a to group I mGluRs.

Muscarinic Receptor–Dependent Long-Term Depression in Rat Visual Cortex Is PKC Independent but Requires ERK1/2 Activation and Protein Synthesis

Intact cholinergic innervation of visual cortex is critical for normal processing of visual information and for spatial memory acquisition and retention. However, a complete description of the mechanisms by which the cholinergic system modifies synaptic function in visual cortex is lacking. Previously it was shown that activation of the m1 subtype of muscarinic receptor induces an activity-dependent and partially N-methyl-d-aspartate receptor (NMDAR)-dependent long-term depression (LTD) at layer 4-layer 2/3 synapses in rat visual cortex slices in vitro. The cellular mechanisms downstream of the Galphaq coupled m1 receptor required for induction of this LTD (which we term mLTD) are currently unknown. Here, we confirm a role for m1 receptors in mLTD induction and use a series of pharmacological tools to study the signaling molecules downstream of m1 receptor activation in mLTD induction. We found that mLTD is prevented by inhibitors of L-type Ca(2+) channels, the Src kinase family, and the mitogen-activated kinase/extracellular kinase. mLTD is also partially dependent on phospholipase C but is unaffected by blocking protein kinase C. mLTD expression can be long-lasting (>2 h) and its long-term maintenance requires translation. Thus we report the signaling mechanisms underlying induction of an m1 receptor-dependent LTD in visual cortex and the requirement of protein synthesis for long-term expression. This plasticity could be a mechanism by which the cholinergic system modifies glutamatergic synapse function to permit normal visual system processing required for cognition.

Dark rearing alters the short-term synaptic plasticity in visual cortex

The strength of all chemical synapses can be rapidly up- or down-regulated by their recent activities to reshape the postsynaptic signal through a mechanism of short-term facilitation or depression. It is also true that sensory experience is essential for maturation of cortical circuits and function. We studied the effect of sensory experience on the short-term plasticity in brain slices of rat visual cortex. Repetitive stimulation was applied in layer II/III and the response of pyramidal neuron in layer V was examined by whole-cell recording. We deprived the visual experience of rats by rearing the animals in dark environment. We found that dark rearing (DR) had no effects on paired-pulse interactions of either excitatory postsynaptic currents (EPSCs) or inhibitory postsynaptic currents (IPSCs). However, DR increased the level of IPSCs steady-state depression at stimulation frequency of 20Hz or more. This result, together with the finding that DR reduced the excitability of neural circuit in visual cortex, suggested a compensatory mechanism, which may be important in enhancing the network excitability at a time when synapses are immature.

Adaptation at Synaptic Connections to Layer 2/3 Pyramidal Cells in Rat Visual Cortex

Neocortical synapses express differential dynamic properties. When activated at high frequencies, the amplitudes of the subsequent postsynaptic responses may increase or decrease, depending on the stimulation frequency and on the properties of that particular synapse. Changes in the synaptic dynamics can dramatically affect the communication between nerve cells. Motivated by this question, we studied dynamic properties at synapses to layer 2/3 pyramidal cells with intracellular recordings in slices of rat visual cortex. Synaptic responses were evoked by trains of test stimuli, which consisted of 10 pulses at different frequencies (5-40 Hz). Test stimulation was applied either without any adaptation (control) or 2 s after an adaptation stimulus, which consisted of 4 s stimulation of these same synapses at 10, 25, or 40 Hz. The synaptic parameters were then assessed from fitting the data with a model of synaptic dynamics. Our estimates of the synaptic parameters in control, without adaptation are broadly consistent with previous studies. Adaptation led to pronounced changes of synaptic transmission. After adaptation, the amplitude of the response to the first pulse in the test train decreased for several seconds and then recovered back to the control level with a time constant of 2-18 s. Analysis of the data with extended models, which include interaction between different pools of synaptic vesicles, suggests that the decrease of the response amplitude was due to a synergistic action of two factors, decrease of the release probability and depletion of the available transmitter. After a weak (10 Hz) adaptation, the decrease of the response amplitude was accompanied by and correlated with the decrease of the release probability. After a strong adaptation (25 or 40 Hz), the depletion of synaptic resources was the main cause for the reduced response amplitude. Adaptation also led to pronounced changes of the time constants of facilitation and recovery, however, these changes were not uniform in all synapses, and on the population level, the only consistent and significant effect was an acceleration of the recovery after a strong adaptation. Taken together, our results suggest, that apart from decreasing the amplitude of postsynaptic responses, adaptation may produce synapse-specific effects, which could result in a kind of re-distribution of activity within neural networks.

Phase sensitivity of synaptic modifications in oscillating cells of rat visual cortex.

Synaptic modifications depend on the amplitude and temporal relations of presynaptic and postsynaptic activation. The interactions among these variables are complex and hard to predict when neurons engage in synchronized high-frequency oscillations in the beta and gamma frequency range, as is often observed during signal processing in the cerebral cortex. Here we investigate in layer II/III pyramidal cells of rat visual cortex slices how synapses change when synchronized, oscillatory multifiber activity impinges on postsynaptic neurons during membrane potential (V(m)) oscillations at 20 and 40 Hz. Synapses underwent long-term potentiation (LTP) when EPSPs coincided with the peaks of the V(m) oscillations but exhibited long-term depression (LTD) when EPSPs coincided with the troughs. The induction of LTP but not of LTD was NMDA receptor dependent, required additional activation of muscarinic receptors in older animals, and persisted in a kainate-driven increased conductance state. Thus, even when neuronal networks engage in high-frequency oscillations, synaptic plasticity remains exquisitely sensitive to the timing of discharges. This is an essential prerequisite for theories which assume that precise synchronization of discharges serves as signature of relatedness in distributed processing.

Silent synapses in the immature visual cortex: layer-specific developmental regulation.

Central glutamatergic synapses are thought to initially form as immature, so-called silent synapses showing exclusively N-methyl-d-aspartate receptor-mediated synaptic transmission. Postsynaptic insertion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors during further development leads to a conversion into functional, mature synapses. Here, we tested the hypothesis that, according to the "inside first-outside last" pattern of neocortical layer formation and synaptogenesis, pyramidal cells in the superficial layers might show a higher fraction of silent synapses compared with pyramidal cells in the deep layers. We performed an electrophysiological analysis of glutamatergic synapses in acute rat visual cortex slices during postnatal development. In layer VI pyramidal neurons the incidence of silent synapses was high during the first postnatal week and strongly declined during further development. Surprisingly, in superficial cortical plate pyramidal neurons (immature layers II/III), the fraction of silent synapses was initially very low and increased up to the second postnatal week. Thereafter, a similar decline as found in layer VI pyramidal neurons was observed. Thus the developmental regulation of silent synapses was clearly different in pyramidal neurons from different neocortical layers. The almost complete absence of silent synapses at early stages in layer II/III pyramidal neurons indicates that an initially formed subset of synapses is constitutively functional. This might be important to enable spontaneous activity and latter activity-dependent maturation of synapses.

Age-dependent emergence of oscillatory signal flow between the primary and secondary visual cortices in rat brain slices

Developmental changes in dynamics of signal propagation between the primary (Oc1) and secondary visual cortex (Oc2) were investigated by using optical recording methods with voltage-sensitive dyes. Propagating oscillatory optical responses were evoked by our previously reported procedure, and were recorded on stimulation to white matter of Oc1 in rat visual cortex slices. In immature slices, evoked signals spread out from the stimulation site by way of deep layers, but were restricted largely to Oc1. In mature slices, however, evoked signals spread upward from the stimulation site at first, and then spread out along layer II/III, finally to penetrate Oc2. More remarkably, after this initial signal was attenuated, oscillatory responses emerged and spread back from Oc2 to Oc1 by way of layer II/III, suggesting that the origin of backpropagating oscillation is located in Oc2. The initial forward component was dependent on both N-methyl- d-aspartate (NMDA) and non-NMDA receptors, and the subsequent backward components were dependent only on NMDA receptors. These results suggest that the extent of corticocoritcal signal propagation within the visual cortex grows wider horizontally during maturation, so that information interchange may become easier between the Oc1 and Oc2.

Rapid eye-movement sleep deprivation does not ‘rescue’ developmentally regulated long-term potentiation in visual cortex of mature rats

The age at which it is possible to obtain a usually age-limited (developmental) form of long-term potentiation (LTP) in rat visual cortex slices can be extended by suppressing rapid eye movement (REM) sleep. In this study, we examined whether REM sleep deprivation can also ‘rescue’ this type of LTP in older rats. Rats, 42–59 days of age, were either REM sleep-deprived for 7–10 days ( n=8), or not deprived of REM sleep (control group, n=8). Brain slices from visual cortex were tested for the developmental form- and a related, non-developmental form of LTP. Three of the eight REM sleep-deprived animals and four of the eight non-deprived animals met criteria for a valid attempt to induce the developmental form of LTP. Though the non-age-regulated form of LTP could be obtained in all seven of these animals, the developmental form could not be elicited in any, indicating that REM sleep deprivation does not uniformly affect all forms of LTP in adult rats. We conclude that extended periods of REM sleep deprivation do not facilitate induction of developmentally regulated LTP once the animal is beyond a certain age.

Synaptic inhibition of pyramidal cells evoked by different interneuronal subtypes in layer v of rat visual cortex.

Properties of GABA(A) receptor-mediated unitary inhibitory postsynaptic currents (uIPSCs) in pyramidal (P) cells, evoked by fast spiking (FS) and low-threshold spike (LTS) subtypes of interneurons in layer V of rat visual cortex slices were examined using dual whole cell recordings. uIPSCs evoked by FS cells were larger and faster rising than those evoked by LTS cells, consistent with the known primary projections of FS and LTS cell axons to perisomatic and distal dendritic areas of layer V pyramidal cells, respectively, and the resulting electrotonic attenuation for LTS-P synaptic events. Unexpectedly, the decay time constants for LTS-P and FS-P uIPSCs were not significantly different. Modeling results were consistent with differences in the underlying GABA(A) receptor-mediated conductance at LTS-P and FS-P synapses. Paired-pulse depression (PPD), present at both synapses, was associated with an increase in failure rate and a decrease in coefficient of variation, indicating that presynaptic mechanisms were involved. Furthermore, the second and first uIPSC amplitudes during PPD were not inversely correlated, suggesting that PPD at both synapses is independent of previous release and might not result from depletion of the releasable pool of synaptic vesicles. Short, 20-Hz trains of action potentials in presynaptic interneurons evoked trains of uIPSCs with exponentially decreasing amplitudes at both FS-P and LTS-P synapses. FS-P uIPSC amplitudes declined more slowly than those of LTS-P uIPSCs. Thus FS and LTS cells, with their differences in firing properties, synaptic connectivity with layer V P cells, and short-term synaptic dynamics, might play distinct roles in regulating the input-output relationship of the P cells.

Activation of Group III mGluRs increases the activity of neurons in area 17 of the cat.

Activation of Group III metabotropic glutamate receptors (mGluRs) by L(+)-2-amino-4-phosphonobutyric acid (L-AP4) has different effects on in vitro slice preparations of visual cortex (Jin & Daw, 1998) as compared with in vivo recordings from somatosensory cortex (Wan & Cahusac, 1995). To investigate the role of Group III mGluRs in the cat visual cortex, in vivo recordings were made of neurons in area 17 of the visual cortex of kittens and adult cats at different ages and the effect of iontophoretic application of L-AP4 (100 mM) was examined. Application of L-AP4 resulted in an increase of the spontaneous activity and visual response of neurons to visual stimulation, the former more than the latter. The effect of L-AP4 was greatest at 3-5 weeks of age with the effect on the visual response declining more rapidly than the effect on spontaneous activity. Consistent with work in rat cortex (Jin & Daw, 1998), the effect of L-AP4 was significantly greater in upper and lower layers than in middle layers. Whole-cell in vitro recordings from slices of rat visual cortex indicated that L-AP4 (50 mM) did not increase the number of spikes elicited by increasing levels of current injections. These results confirm that L-AP4 increases activity in vivo and reasons for the discrepancy with the in vitro results are discussed.

Metabotropic glutamate receptors mediate expression of LTP in slices of rat visual cortex.

Long-term-potentiation (LTP) can be induced by application of a standard theta-burst stimulation protocol in slice preparations of the neocortex. This type of LTP is known to be dependent on the activation of NMDA receptors. The present study used specific experimental conditions to evoke a non-NMDA receptor mediated type of LTP. By use of weak theta-burst stimulation (wTBS) we describe a non-NMDA receptor dependent LTP in rat visual cortex in vitro, which is sensitive to an antagonist of metabotropic glutamate receptors (mGluR). In slices of the visual cortex we stimulated ascending inputs in cortical layer IV and recorded extracellular field potentials (FPs) from cortical layers II/III. In disinhibited slices (with 1 microm picrotoxin), a wTBS induced LTP to 138% of control. The expression of this potentiation was insensitive to the NMDA-receptor antagonist, D-AP5, but could be abolished by application of the mGluR antagonist MCPG. These data suggest an NMDA-independent mechanism for LTP induction in the visual cortex which can be observed in layer II/III neurons.

A distinct form of calcium release down-regulates membrane excitability in neocortical pyramidal cells

We reported a novel type of calcium release from inositol-1,4,5-trisphosphate (IP 3)-sensitive calcium stores synergistically induced by muscarinic acetylcholine receptor (mAchR)-mediated increase in IP 3 and action potential-induced calcium influx (IP 3-assisted calcium-induced calcium release, IP 3-assisted CICR). To clarify its functional significance, the effects of IP 3-assisted CICR on spike-frequency adaptation were examined in layer II/III neurons from rat visual cortex slices. IP 3-assisted CICR was enabled with a high concentration of the mAchR agonist carbachol (10 μM). The magnitude of this CICR was the more augmented at higher firing frequencies. With 10 μM carbachol, spike-frequency adaptation was reduced for spike trains at ‘low’ firing frequencies (6–10 Hz), but was rather enhanced at ‘high’ firing rates (16–22 Hz): excitability was down-regulated at ‘high’ frequencies. With 1 μM carbachol, by contrast, IP 3-assisted CICR failed to occur, and spike-frequency adaptation was always reduced at any spike frequencies. Intracellular injection of the IP 3 receptor blocker heparin prevented both the mAchR-mediated occurrence of IP 3-assisted CICR and enhancement of spike-frequency adaptation with 10 μM carbachol. Both of these mAchR-mediated effects were reproduced by intracellular IP 3 injection, and were shown to be associated with each other by simultaneous recordings of membrane potential and intracellular calcium increase. We propose that IP 3-assisted CICR offers a novel way to protect these cortical neurons from hyperexcitability and presumably from excitotoxic cell death.

Effect of the group I metabotropic glutamate agonist DHPG on the visual cortex.

Metabotropic glutamate receptors have a variety of effects in visual cortex that depend on the age of the animal, the layer of the cortex, and the group of the receptor. Here we describe these effects for group I receptors, using both in vivo and in vitro preparations. The metabotropic group I glutamate receptor agonist 3,5 dihydroxyphenylglycine (DHPG) potentiates the responses to N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in slices of rat visual cortex. It also increases, initially, the visual response in the cat visual cortex. Both these effects are largest at 3-4 wk of age and decline to insignificance by 10 wk of age. Both are also largest in lower layers of cortex, which explains why the facilitatory effects found with the general metabotropic glutamate agonist 1S,3R aminocyclopentane-1,3-dicarboxylic acid (ACPD) are observed only in lower layers. Prolonged application of DHPG in the cat visual cortex, after the initial excitatory effect, produces depression. We also found that DHPG facilitates the NMDA response in fast-spiking cells, which are inhibitory, providing a partial explanation for this. Thus there are multiple effects of group I metabotropic glutamate receptors, which vary with layer and age in visual cortex.

Increased synaptic plasticity in the surround of visual cortex lesions in rats.

Lesion-induced functional loss is reduced when new synaptic connections are established in the surround of a cortical lesion. For this, long-term synaptic plasticity can play a key role. We studied long-term potentiation (LTP) and long-term depression (LTD) in slices of rat visual cortex with small cortical lesions. Surprisingly, the normal balance between LTP and LTD was significantly altered in the first week following cortical injury. Theta-burst induced LTP was increased, whereas LTD evoked by low frequency stimulation was not affected. The increased potentiation of subcortical inputs after cortical lesions opens a window for facilitated early functional reorganization by repetitive visual training.

Synchronized population oscillation of excitatory synaptic potentials dependent of calcium-induced calcium release in rat neocortex layer II/III neurons

We examined the roles played by calcium-induced calcium release from ryanodine-sensitive calcium stores in induction of neocortical membrane potential oscillation by using caffeine, an agonist of ryanodine receptors. Intracellular recordings were made from neurons in layer II/III of rat visual cortex slices in a caffeine-containing medium. White matter stimulation initially evoked monophasic synaptic potentials. As low-frequency stimulation continued for over 10 min, an oscillating synaptic potential gradually became evoked, in which a paroxysmal depolarization shift was followed by a 8–10-Hz train of several depolarizing wavelets. This oscillating potential was not induced in a medium containing no caffeine with 2 or 0.5 mM [Mg 2+] o. Under blockade of N-methyl- d-aspartate receptors, induction of this oscillating potential failed even with caffeine application. Experiments with the calcium store depletor, thapsigargin, revealed that this oscillating potential is induced in a manner dependent on intracellular calcium release. Dual intracellular recordings revealed that the oscillation was synchronized in pairs of layer II/III neurons. The oscillating potential was detectable by field potential recordings also, suggesting that the present oscillation seems to reflect a network property.

Structure and projections of white matter neurons in the postnatal rat visual cortex.

Transient contributions of subplate neurons to the initial development of the cortex are well-characterized, yet little data are available on a subpopulation of subplate neurons that persist in the white matter (WM) of the cerebral cortex across development. To characterize the WM neurons, differential interference contrast and Nomarski optics were used to visualize individual cells in the WM in slices of rat visual cortex at postnatal ages 9-23. Soma-dendritic morphology and local axonal projection patterns, including probable synaptic innervation sites of their axons, were identified by intracellular filling with biocytin during electrophysiologic recordings. Dendritic branches of all WM neurons, tripartitioned here into upper, middle, and deep divisions, extend throughout the WM and frequently into the overlying cortex. Axonal arborizations from most WM neurons, including apparent boutons, project into adjacent WM with many also innervating overlying cortical layers, whereas some project into the stratum oriens/alveus of the hippocampal formation. Processes of a subset of WM neurons appear to be confined to the WM itself. By using antimicrotubule associated protein (MAP2) immunostaining to quantify the density of WM neurons in rat visual cortex, we find that their overall numbers decrease to approximately 30% of initial levels during postnatal development. During this same developmental period, an increasing percentage of WM neurons contain the synthetic enzyme for nitric oxide, nitric oxide synthase (NOS), as evaluated by immunostaining. Thus, WM neurons that survive the initial perinatal period of cell death are positioned under the laminae of the maturing cortex to potentially modulate the integration of visual signals through either conventional synaptic or nonconventional (diffusible NO signaling) mechanisms.