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B W Connors

Publications and source records attributed to B W Connors.

At least 19 recordsLinked to original sources
PubMed1999

Two networks of electrically coupled inhibitory neurons in neocortex.

Inhibitory interneurons are critical to sensory transformations, plasticity and synchronous activity in the neocortex. There are many types of inhibitory neurons, but their synaptic organization is poorly understood. Here we describe two functionally distinct inhibitory networks comprising either fast-spiking (FS) or low-threshold spiking (LTS) neurons. Paired-cell recordings showed that inhibitory neurons of the same type were strongly interconnected by electrical synapses, but electrical synapses between different inhibitory cell types were rare. The electrical synapses were strong enough to synchronize spikes in coupled interneurons. Inhibitory chemical synapses were also common between FS cells, and between FS and LTS cells, but LTS cells rarely inhibited one another. Thalamocortical synapses, which convey sensory information to the cortex, specifically and strongly excited only the FS cell network. The electrical and chemical synaptic connections of different types of inhibitory neurons are specific, and may allow each inhibitory network to function independently.

Action Potentials↗
PubMed1999

Sensory experience modifies the short-term dynamics of neocortical synapses.

Many representations of sensory stimuli in the neocortex are arranged as topographic maps. These cortical maps are not fixed, but show experience-dependent plasticity. For instance, sensory deprivation causes the cortical area representing the deprived sensory input to shrink, and neighbouring spared representations to enlarge, in somatosensory, auditory or visual cortex. In adolescent and adult animals, changes in cortical maps are most noticeable in the supragranular layers at the junction of deprived and spared cortex. However, the cellular mechanisms of this experience-dependent plasticity are unclear. Long-term potentiation and depression have been implicated, but have not been proven to be necessary or sufficient for cortical map reorganization. Short-term synaptic dynamics have not been considered. We developed a brain slice preparation involving rat whisker barrel cortex in vitro. Here we report that sensory deprivation alters short-term synaptic dynamics in both vertical and horizontal excitatory pathways within the supragranular cortex. Moreover, modifications of horizontal pathways amplify changes in the vertical inputs. Our findings help to explain the functional cortical reorganization that follows persistent changes of sensory experience.

Animals↗
PubMed1999

Efficacy of thalamocortical and intracortical synaptic connections: quanta, innervation, and reliability.

Thalamocortical (TC) synapses carry information into the neocortex, but they are far outnumbered by excitatory intracortical (IC) synapses. We measured the synaptic properties that determine the efficacy of TC and IC axons converging onto spiny neurons of layer 4 in the mouse somatosensory cortex. Quantal events from TC and IC synapses were indistinguishable. However, TC axons had, on average, about 3 times more release sites than IC axons, and the mean release probability at TC synapses was about 1.5 times higher than that at IC synapses. Differences of innervation ratio and release probability make the average TC connection several times more effective than the average IC connection, and may allow small numbers of TC axons to dominate the activity of cortical layer 4 cells during sensory inflow.

Animals↗
PubMed1999

Epileptiform propagation patterns mediated by NMDA and non-NMDA receptors in rat neocortex.

PURPOSE: The neocortex can generate various forms of epileptiform activity, including one that depends on N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs), and another dependent on non-NMDA-type (AMPA) glutamate receptors (AMPARs). Previous work in vitro suggests that both forms of activity are initiated by neurons of layer 5, but the spatial patterns of horizontal propagation have been studied only for the AMPAR form. We have tested the hypothesis that both types of epileptiform activity spread via common pathways in one cortical layer, suggesting that lamina-specific intervention might selectively interrupt both. METHODS: Slices of rat somatosensory cortex were maintained in vitro and treated with the gamma-aminobutyric acid type A (GABA(A))-receptor antagonist picrotoxin. Single all-or-none epileptiform discharges were evoked with an electrical stimulus, and extracellular microelectrodes were used to track the vertical and lateral spread of the discharges. RESULTS: In both high and low concentrations of picrotoxin, the non-NMDAR antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) completely blocked propagation, whereas the NMDAR antagonist D-2-amino-5-phosphonovaleric acid (DAPV) only shortened the duration of discharges. When extracellular [Mg2+] was reduced in the presence of picrotoxin and CNQX, NMDAR-dependent epileptiform discharges could be initiated. NMDAR-dependent discharges spread at about one fifth the conduction velocity of AMPAR-dependent events. Analysis of spatiotemporal field-potential patterns suggested that both NMDAR- and AMPAR-mediated propagation involved early activity in layers 5 and 6, followed by larger-amplitude activity in upper cortical layers along the path of propagation. CONCLUSIONS: Our results imply that a common pathway mediates the propagation of these two forms of epileptiform activity, and suggests that lamina-specific surgical intervention might maximize anticonvulsant effect while minimally disrupting cortical function.

2-Amino-5-phosphonovalerate↗
PubMed1999

Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in the rat barrel cortex.

We have used whole cell recording in the anesthetized rat to study whisker-evoked synaptic and spiking responses of single neurons in the barrel cortex. On the basis of their intrinsic firing patterns, neurons could be classified as either regular-spiking (RS) cells, intrinsically burst-spiking (IB) cells, or fast-spiking (FS) cells. Some recordings responded to current injection with a complex spike pattern characteristic of apical dendrites. All cell types had high rates of spontaneous postsynaptic potentials, both excitatory (EPSPs) and inhibitory (IPSPs). Some spontaneous EPSPs reached threshold, and these typically elicited only single action potentials in RS cells, bursts of action potentials in FS cells and IB cells, and a small, fast spike or a complex spike in dendrites. Deflection of single whiskers evoked a fast initial EPSP, a prolonged IPSP, and delayed EPSPs in all cell types. The intrinsic firing pattern of cells predicted their short-latency whisker-evoked spiking patterns. All cell types responded best to one or, occasionally, two primary whiskers, but typically 6-15 surrounding whiskers also generated significant synaptic responses. The initial EPSP had a relatively fixed amplitude and latency, and its amplitude in response to first-order surrounding whiskers was approximately 55% of that induced by the primary whisker. Second- and third-order surrounding whiskers evoked responses of approximately 27 and 12%, respectively. The latency of the initial EPSP was shortest for the primary whiskers, longer for surrounding whiskers, and varied with the neurons' depth below the pia. EPSP latency was shortest in the granular layer, longer in supragranular layers, and longest in infragranular layers. The receptive field size, defined as the total number of fast EPSP-inducing whiskers, was independent of each cell's intrinsic firing type, its subpial depth, or the whisker stimulus parameters. On average, receptive fields included >10 whiskers. Our results show that single neurons integrate rapid synaptic responses from a large proportion of the mystacial vibrissae, and suggest that the whisker-evoked responses of barrel neurons are a function of both synaptic inputs and intrinsic membrane properties.

Animals↗
PubMed1998

Backward cortical projections to primary somatosensory cortex in rats extend long horizontal axons in layer I.

We have studied the origin and extent of axons within layer I of the primary somatosensory cortex (SI) of rats by using retrograde and anterograde tracers with an emphasis on reciprocal connections to layer I of SI from ipsilateral cortical areas that are the target of SI projections. Small crystals of 1,1',dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) labeled horizontal axons projecting in all directions within layer I, which extended for up to 4 mm with numerous terminal branches. Applications of horseradish peroxidase, Diamidino yellow, or fast blue to the pial surface of SI labeled a characteristic pattern of neurons below the application site that excluded neurons in layer IV of the barrel fields, unless the dye penetrated deeper than layer II. This provided a control for the effective depth of the layer I dye applications. Retrograde transport from layer I of SI was traced to the primary motor area, the lateral parietal areas, including the secondary somatosensory (SII) and agranular insular cortex ipsilaterally, as well as the homotopic areas of SI contralaterally. Injections of the anterograde tracer dextran amine at the same site as the SI surface application labeled dense fiber terminations in middle layers of these same secondary areas in the primary motor cortex (MI) or SII in the midst of cells labeled by retrograde transport from layer I of SI. Injections of dextran amine into these secondary cortical areas labeled fibers that coursed through deep layers to SI, where they ascended to layer I. These reciprocal corticocortical inputs to SI were concentrated in layer I, where they branched and extended horizontally across several SI barrels.

Animals↗
PubMed1998

Layer-specific pathways for the horizontal propagation of epileptiform discharges in neocortex.

PURPOSE: Epileptiform discharges that resemble interictal spikes can be generated by slices of neocortex treated with antagonists of gamma-aminobutyric acid A (GABA(A)) receptors. These discharges can propagate horizontally for long distances. We tested the hypothesis that propagation occurs through preferred horizontal pathways that lie in a particular cortical layer. METHODS: Slices were prepared from the primary somatosensory cortex of rats, maintained in vitro, and bathed with the GABA(A) receptor antagonist picrotoxin. Electrical stimuli were used to evoke single all-or-none paroxysmal field potentials (PFP) that were recorded with pairs or arrays of field potential electrodes. RESULTS: To test which laminae are necessary for propagation, vertical cuts were made to force the PFP to spread horizontally through particular layers. If slices were bathed in a high dose of picrotoxin (35 microM), a bridge of cortex 350 microm thick placed at any lamina was sufficient to support PFP propagation. However, in low picrotoxin doses (2.5 microM), similarly sized bridges had to include tissue from layers 4/5 or 5/6 to support propagation. When slices were cut horizontally (i.e., parallel to the pia) in strips. either upper-, middle-, or lower-layer strips were sufficient to support PFP propagation if the picrotoxin concentration was high; however, in low picrotoxin doses, only horizontal strips that included layer 5 could support propagation. Finally, in intact picrotoxin-treated slices, focal applications of GABA were systematically applied to different laminae as the PFP propagated past; GABA was most effective at blocking or delaying propagation when it was applied to layer 5b. CONCLUSIONS: We conclude that epileptiform propagation can occur through a variety of horizontal pathways when cortical inhibition is strongly impaired. However, when inhibition is reduced only moderately, axonal pathways in layer 5 are critical for seizure spread.

Animals↗
PubMed1997

Distinct forms of short-term plasticity at excitatory synapses of hippocampus and neocortex.

The expression of short- and long-term synaptic plasticity varies strongly across pathways in the central nervous system. Differences in the properties of transmitter release may underlie some of this variability. Here we compared the short-term plasticity displayed by a neocortical and a hippocampal pathway in vitro, and observed dramatic differences. Conditions known to increase transmitter release probability were more effective in hippocampus, while conditions known to decrease release probability were similarly effective in both pathways. The effects of the irreversible open-channel blocker of N-methyl-D-aspartate receptors, MK-801, implied that synapses in the neocortical pathway have a relatively high probability of transmitter release as compared with synapses in the hippocampal pathway. Differences in release probability may explain the pathway-specific variance in short- and long-term synaptic plasticity.

Animals↗
PubMed1997

Thalamocortical synapses.

Thalamocortical synapses inform the cerebral neocortex about the external and internal worlds. The thalamus produces myriad thalamocortical pathways that vary in morphological, physiological, pharmacological and functional properties. All these features are of great importance for understanding how information is acquired, integrated, processed, stored and retrieved by the thalamocortical system. This paper reviews the properties of the afferents from thalamus to cortex, and identifies some of the gaps in our knowledge of thalamocortical pathways.

Animals↗
PubMed1997

Differential regulation of neocortical synapses by neuromodulators and activity.

Synapses are continually regulated by chemical modulators and by their own activity. We tested the specificity of regulation in two excitatory pathways of the neocortex: thalamocortical (TC) synapses, which mediate specific inputs, and intracortical (IC) synapses, which mediate the recombination of cortical information. Frequency-sensitive depression was much stronger in TC synapses than in IC synapses. The two synapse types were differentially sensitive to presynaptic neuromodulators: only IC synapses were suppressed by activation of GABA(B) receptors, only TC synapses were enhanced by nicotinic acetylcholine receptors, and muscarinic acetylcholine receptors suppressed both synapse types. Modulators also differentially altered the frequency sensitivity of the synapses. Our results suggest a mechanism by which the relative strength and dynamics of input and associational pathways of neocortex are regulated during changes in behavioral state.

Animals↗
PubMed1996

Neuronal firing: does function follow form?

Neurons generate diverse firing patterns to perform a range of specialized tasks. Experiments show that many features of these firing patterns arise from distinctive membrane properties, but theoretical work predicts that differences in neuronal morphology are also important.

Animals↗
PubMed1996

Cellular mechanisms of the augmenting response: short-term plasticity in a thalamocortical pathway.

Some thalamocortical pathways display an "augmenting response" when stimuli are delivered at frequencies between 7 and 14 Hz. Cortical responses to the first three stimuli of a series increase progressively in amplitude and are relatively stable thereafter. We have investigated the cellular mechanisms of the augmenting response using extracellular and intracellular recordings in vivo and in slices of the sensorimotor neocortex of the rat. Single stimuli to the ventrolateral (VL) nucleus of the thalamus generate EPSPs followed by feedforward IPSPs that hyperpolarize cells in layer V. A long-latency depolarization interrupts the IPSP with a peak at approximately 200 msec. A second VL stimulus delivered during the hyperpolarization and before the peak of the long-latency depolarization yields an augmenting response. The shortest latency for augmenting responses occurs in cells of layer V, and they appear in dendrites and somata recorded in upper layers approximately 5 msec later. Recordings in vitro show that some layer V cells have hyperpolarization-activated and deinactivated conductances that may serve to increase their excitability after IPSPs. Also in vitro, cells from layer V, but not from layer III, generated augmenting responses at the same stimulation frequencies that were effective in vivo. Control experiments indicated that neither paired-pulse depression of IPSPs nor presynaptically mediated facilitation can account for the augmenting response. Active dendritic conductances contribute to the spread of augmenting responses into upper layers by way of back-propagating fast spikes, which attenuate with repetition, and long-lasting spikes, which enhance in parallel with the augmenting response. In conclusion, we propose that the initiation of augmenting responses depends on an interaction between inhibition, intrinsic membrane properties, and synaptic interconnections of layer V pyramidal neurons.

Animals↗
PubMed1996

Laminar origins of inhibitory synaptic inputs to pyramidal neurons of the rat neocortex.

1. Inhibitory neuron-pyramidal cell interactions were investigated in slices of rat somatosensory cortex in which excitatory synaptic transmission was blocked with bath-applied glutamate receptor antagonists. Local inhibitory neurons were excited by focal pressure ejections of small (approximately 40 pl) volumes of 1-10 mM acetylcholine. 2. The frequency of inhibitory postsynaptic potentials (IPSPs) ("responses per trial' or R/T) declined as the stimulation distance was increased. Inhibitory inputs were most prevalent in layer II/III regular spiking (RS) pyramidal neurons (30 cells) where median R/T was 0.020. In layer V, the median R/T was 0.024 for RS neurons (25 cells), but significantly lower for burst-firing (IB) neurons (17 cells), where median R/T was 0.007 (P = 0.039). 3. IPSPs in individual layer V pyramidal cells were recorded with CsCl electrodes. In eight neurons, spontaneous picrotoxin-sensitive IPSPs were recorded and found to display a wide range of 10-90% rise times (1-34 ms), not correlated with amplitude (0.2-18 mV). For a further ten pyramidal neurons, extracellular stimulating electrodes were placed simultaneously in layers II/III and V/VI in order to evoke pairs of IPSPs whose waveforms were averaged and compared. In seven cells, IPSPs evoked from layer II/III (distal location) had longer 10-90% rise times than IPSPs evoked from layer V/VI stimulating electrodes (proximal location). In addition, "proximal' IPSPs could always be reversed by membrane depolarization whereas "distal' ones could not (n = 4/4). 4. This study showed that pyramid cell-inhibitory neuron interconnections are extensive but their spatial organization varies with cell class and with cortical layer. In addition, pyramidal neurons can receive inhibitory inputs from locations on their apical dendrites.

Acetylcholine↗
PubMed1996

Spatiotemporal properties of short-term plasticity sensorimotor thalamocortical pathways of the rat.

Each region of neocortex receives synaptic input from several thalamic nuclei, but the response properties of thalamocortical pathways may differ. We have studied the frontoparietal (motor and somatosensory) neocortex of the rat and have examined the responses induced by stimulating two convergent thalamocortical projections originating in the ventrolateral (VL) nucleus and ventroposterior lateral (VPL) nucleus. Depth recordings and current-source density (CSD) analysis revealed two primary responses with different laminar and temporal patterns when VL and VPL were stimulated. Single shocks to VL produced a characteristic small current sink in layer V, which strongly enhanced in response to a second pulse delivered within a 50-200 msec interval (i.e., the augmenting response). In contrast, a shock to VPL evoked a large current sink that originated in layer IV, spread strongly into the supragranular layers, and was almost abolished in response to a second pulse at intervals of <200 msec (i.e., the decremental response). Control experiments determined that these responses could not be attributed to the antidromic firing of corticothalamic cells, intrathalamic mechanisms, or anesthesia. Topographic response maps were obtained from a grid of 30 sites across frontoparietal cortex. One shock to VL excited a very limited cortical region, but an augmenting response evoked 50-200 msec later spread at approximately 1 m/sec to synchronize the activity across an area up to 25 times larger. In contrast, a single shock to VPL activated a relatively large area, but the area activated by a second shock delivered within 200 msec was much smaller. We conclude that overlapping thalamocortical projections, originating in different thalamic nuclei, have distinct spatiotemporal response characteristics that may serve the functional specializations of these pathways.

Animals↗
PubMed1996

Short-term plasticity of a thalamocortical pathway dynamically modulated by behavioral state.

The neocortex receives information about the environment and the rest of the brain through pathways from the thalamus. These pathways have frequency-dependent properties that can strongly influence their effect on the neocortex. In 1943 Morison and Dempsey described "augmenting responses," a form of short-term plasticity in some thalamocortical pathways that is triggered by 8- to 15-hertz activation. Results from anesthetized rats showed that the augmenting response is initiated by pyramidal cells in layer V. The augmenting response was also observed in awake, unrestrained animals and was found to be dynamically modulated by their behavioral state.

Animals↗
PubMed1996

Short-term synaptic enhancement and long-term potentiation in neocortex.

Repetitive stimuli reliably induce long-term potentiation (LTP) of synapses in the upper layers of the granular somatosensory cortex but not the agranular motor cortex of rats. Herein we examine, in these same cortical areas, short-term changes in synaptic strength that occur during the LTP induction period. theta-Burst stimulation produced a strong short-term enhancement of synapses in the granular area but only weak enhancement in the agranular area. The magnitude of enhancement during stimulation was strongly correlated with the magnitude of LTP subsequently expressed. Short-term enhancement was abolished by an antagonist of N-methyl-D-aspartate (NMDA) receptors but remained in the presence of a non-NMDA receptor antagonist. Inhibitory postsynaptic potentials of the granular and agranular areas displayed similar frequency sensitivity, but the frequency sensitivity of NMDA receptor-dependent excitatory postsynaptic potentials differed significantly between areas. We propose that pathway-specific differences in short-term enhancement are due to variations in the frequency dependence of NMDA currents; different capacities for short-term enhancement may explain why repetitive stimulation more readily induces LTP in the somatosensory cortex than in the motor cortex.

2-Amino-5-phosphonovalerate↗
PubMed1996

Two types of network oscillations in neocortex mediated by distinct glutamate receptor subtypes and neuronal populations.

1. Two distinct forms of spontaneous synchronous oscillations were investigated with field potential recordings in slices of rat somatosensory cortex in vitro. 2. The first type of synchronous oscillation was activated by low extracellular [Mg2+] and had dominant frequencies of 8-12 Hz. It was abolished reversibly by the N-methyl-D-aspartate (NMDA) receptor antagonists D-2-amino-5-phosphonovaleric acid and was relatively unaffected by the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). The duration of oscillatory events was increased by blocking gamma-aminobuturic acid-A receptors with bicuculline or by activating metabotropic glutamate receptors with trans-1-aminocyclopentane-1,3-dicarboxylic acid. 3. A second form of synchronous oscillation was activated by acute application of kainic acid (10 microM), had dominant frequencies of 1-5 Hz, and was abolished reversibly by DNQX. Low concentrations of domoic acid mimicked the effects of kainate, but alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid or quisqualic acid did not, suggesting a role for the GluR5-7 and KA1-2 glutamate receptor subunits. 4. Surgical isolation of cortical layers showed that spontaneous NMDA receptor-dependent oscillations originated within layer 5 exclusively, but kainate receptor-dependent oscillations were uniquely generated by neurons in layers 2/3. 5. Our results suggest that neocortical neurons in layers 2/3 and layer 5 can independently generate two distinct forms of rhythmic population activity, each dependent upon activation of a different subtype of glutamate receptor.

2-Amino-5-phosphonovalerate↗