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B W Connors

Publications and source records attributed to B W Connors.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1995

Inhibitory control of excitable dendrites in neocortex.

1. Many dendrites of pyramidal cells in mature neocortex express active Na+ and Ca2+ conductances. Dendrites are also the target of numerous inhibitory synapses. We examined the interactions between the intrinsic excitability of dendrites and synaptic inhibition using whole cell recordings from the apical dendrites of layer 5 pyramidal cells. Experiments were performed on slices of somatosensory cortex from mature rats. Slices were bathed in the glutamate receptor antagonists 2-amino-5-phosphonopentanoic acid and 6,7-dinitroquinoxaline-2,3-dione, and maintained at 32-36 degrees C. 2. In agreement with previous findings, intradendritic current injection evoked two distinct types of dendritic firing. Type I dendrites generated monophasic fast spikes, whereas type II dendrites showed more complex firing patterns, consisting of fast and slow spike components. 3. Stimulation of cortical layers 2/3 evoked fast inhibitory postsynaptic potentials (IPSPs) in all dendrites tested. IPSP reversal potentials were bimodally distributed, with means of about -53 and -85 mV when recorded with high-Cl(-)-concentration-filled electrodes. Interestingly, IPSP reversal potentials were correlated with the type of dendritic spiking pattern. 4. IPSPs were able to delay, completely block, or partially block spiking in dendrites, depending on the relative timing between inhibition and dendritic spiking. Slow, Ca(2+)-dependent spike components could be blocked selectively by IPSPs. Furthermore, inhibition could either phase advance or phase delay repetitive patterns of dendritic spiking, depending on the timing of the IPSP.

Animals↗
PubMed1995

Different forms of synaptic plasticity in somatosensory and motor areas of the neocortex.

We have studied vertical synaptic pathways in two cytoarchitectonically distinct areas of rat neocortex--the granular primary somatosensory (SI) area and the agranular primary motor (MI) area--and tested their propensity to generate long-term potentiation (LTP), long-term depression (LTD), and related forms of synaptic plasticity. Extracellular and intracellular responses were recorded in layer II/III of slices in vitro while stimulating in middle cortical layers (in or around layer IV). Under control conditions, 5 Hz theta-burst stimulation produced LTP in the granular area, but not in the agranular area. Agranular cortex did generate short-term potentiation that decayed within 20 min. Varying the inter-burst frequency from 2 Hz to 10 Hz reliably yielded LTP of 21-34% above control levels in granular cortex, but no lasting changes were induced in agranular cortex. However, the agranular cortex was capable of generating LTP if a GABAA receptor antagonist was applied locally at the recording site during the induction phase. In contrast to LTP, an identical form of homosynaptic LTD could be induced in both granular and agranular areas by applying low frequency stimulation (1 Hz for 15 min) to the middle layers. Under control conditions, both LTP and LTD were synapse-specific; theta-burst or low-frequency stimulation in the vertical pathway did not induce changes in responses to stimulation of a layer II/III horizontal pathway. Application of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (AP5) blocked the induction of both LTP and LTD in granular and agranular cortex. In the presence of AP5, low-frequency conditioning stimuli yielded a short-term depression in both areas that decayed within 10-15 min. Nifedipine, which blocks L-type, voltage-sensitive calcium channels, slightly depressed the magnitudes of LTP and LTD but did not abolish them. Synaptic responses evoked during theta-burst stimulation were strikingly different in granular and agranular areas. Responses in granular cortex were progressively facilitated during each sequence of 10 theta-bursts, and from sequence-to-sequence; in contrast, responses in agranular cortex were stable during an entire theta-burst tetanus. The results suggest that vertical pathways in primary somatosensory cortex and primary motor cortex express several forms of synaptic plasticity. They were equally capable of generating LTD, but the pathways in somatosensory cortex much more reliably generated LTP, unless inhibition was reduced. LTP may be more easily produced in sensory cortex because of the pronounced synaptic facilitation that occurs there during repetitive stimulation of the induction phase.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Synaptic physiology of horizontal afferents to layer I in slices of rat SI neocortex.

Layer I is a dense synaptic zone ubiquitous in cerebral cortex. Here we describe a novel in vitro preparation of rat somatosensory (SI) neocortical slices that isolates the fibers that extend horizontally through layer I, and allows intracellular and extracellular analysis of synaptic input to dendrites in layer I. Current source-density analysis of this isolated horizontal layer I input reveals monophasic current sinks restricted to layer I and the most superficial part of layer II. The layer I synaptic response of each neuron was correlated with its morphology by filling penetrated cells with biocytin. All filled cells that responded to horizontal layer I inputs were pyramidal neurons in layers II, III, or V with distal apical dendrites in layer I. There was no evidence of antidromic activation from isolated layer I stimulation, and HRP injected into layer I was not transported via the isolated layer I pathway to cortical neurons within the slice. Therefore, this preparation provides a unique way to study an extrinsic synaptic input localized to the most distal apical dendrites of many pyramidal neurons. In contrast to the EPSP-IPSP sequence characteristically evoked by deep layer stimulation, horizontal layer I inputs evoked long-lasting EPSPs (approximately 50 msec); IPSPs were observed only rarely, in the most superficial neurons. Horizontal layer I-evoked EPSPs were blocked by the non-NMDA glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. Consistent with the very distal site of layer I inputs to layer V pyramidal neurons, the amplitudes of initial EPSPs were insensitive to manipulations of the somatic membrane potential. However, these distal EPSPs were greatly attenuated when combined with IPSPs evoked by deep layer stimulation, indicating that the proximal inputs may modulate distal EPSPs with shunting inhibition. In many layer V neurons, the initial EPSP evoked by horizontal layer I stimulation was followed by a variable late depolarization that was blocked by the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid. Since these late depolarizations were enhanced by somatic depolarization and abolished by hyperpolarization, they appeared to be generated postsynaptically at a site more proximal than the initial EPSP that was insensitive to these manipulations. Synaptic inputs to the distal tufts of pyramidal neurons may trigger active currents along the apical dendrites that amplify the EPSP on its way to the soma.

2-Amino-5-phosphonovalerate↗
PubMed1993

Apical dendrites of the neocortex: correlation between sodium- and calcium-dependent spiking and pyramidal cell morphology.

Apical dendrites and somata of layer V pyramidal neurons were recorded with tight-seal patch electrodes in a slice preparation of rat somatosensory cortex. Recording sites were confirmed by measurements of the electrode location and by staining with biocytin. Dendritic recordings were made along the main trunk of the apical dendrite, usually within layer IV, at distances from 100 to 500 microns from the soma. Most cells recorded through the dendrite had a distinct enlargement of the apical trunk around the presumed recording site. The electrical properties of apical dendrites were readily distinguishable from those of somata. Dendrites generated two types of response when injected with depolarizing current. Group I responses were relatively small and broad Na(+)-dependent action potentials whose amplitude and rate-of-rise were negatively correlated with recording distance from the soma. Group II responses were complex, clustered firing patterns of Na(+)-dependent spikes together with higher-threshold slow spikes or plateaus; in these dendrites spike parameters were not correlated with distance from the soma. These two response groups were correlated with dendritic morphology: group I had significantly fewer oblique branches on the apical dendrite (5.5 vs 12.0) and a thinner apical trunk (2.0 vs 2.5 microns) than group II. TTX (1-2 microM) selectively blocked fast dendritic spikes, but not slow spikes and plateaus. Blocking Ca2+ currents reduced complex firing patterns and suppressed high-threshold slow spikes. Physiological and pharmacological studies imply that slow spikes and plateau potentials were primarily generated by high-threshold Ca2+ channels in the apical dendrite. Stimulating axons of layer I elicited EPSPs on distal apical dendrites of layer V cells. Recordings from both groups of apical dendrites revealed that EPSPs triggered a variety of distally generated, all-or-nothing depolarizations. The results show that voltage-dependent Na+ and Ca2+ currents are present in distal apical dendrites, in variable densities. These currents significantly modify distal synaptic events. The prevalence and character of active dendritic spiking (and presumably of Na+ and Ca2+ channel densities) correlate with the morphology of the apical dendritic tree.

Action Potentials↗
PubMed1992

Long-term potentiation in slices of kitten visual cortex and the effects of NMDA receptor blockade.

1. A slice preparation was used to study layer III field potentials (FPs) evoked by electrical stimulation of the white matter-layer VI border and their potentiation by patterned stimuli. 2. The dependence of the FP on recording position was investigated. The maximum field was recorded in layer III at a position radial to the site of stimulation. Because this negative FP reflects an excitatory synaptic current sink, this site was chosen for all subsequent experiments. 3. Under normal recording conditions, components of the layer III FP with latencies greater than 3 ms were completely abolished by kynurenate but unaffected by 2-amino-5-phosphonovalerate (AP5), indicating that this potential reflects the activation of non-NMDA excitatory amino acid receptors. 4. Addition of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline methiodide (BMI) broadened the field potential and revealed an AP5-sensitive component. By filling the recording pipette with BMI, it was possible to substantially reduce inhibition locally around the recording site while avoiding stimulus-driven and spontaneous epileptiform activity. 5. Tetanic stimulation elicited a long-term potentiation (LTP) of the FP in 14 of 17 experiments when the BMI-filled pipette method was used. 6. Addition of 100 microM D,L-AP5 significantly reduced the average probability and magnitude of LTP. Nonetheless, in 2 of 8 experiments, significant LTP was observed after a tetanus in the presence of AP5. Control experiments confirmed that this concentration of AP5 was sufficient to maximally block cortical NMDA receptors. 7. We conclude that LTP of layer III field potentials can be reliably elicited, provided that GABAA-receptor mediated inhibition is blocked locally at the site of recording and that NMDA receptors are recruited during the conditioning stimulation. However, activation of NMDA receptors is apparently not an obligatory step for the induction of use-dependent increases in synaptic strength in the kitten striate cortex.

2-Amino-5-phosphonovalerate↗
PubMed1992

Correlation between intrinsic firing patterns and thalamocortical synaptic responses of neurons in mouse barrel cortex.

We used a thalamocortical slice preparation to record both spike trains and synaptically evoked responses from neurons of mouse barrel cortex. Cells were classified as regular spiking (RS), intrinsically bursting (IB), or fast spiking (FS) according to their temporal firing patterns when injected with current. RS cells were further separated into two subtypes, RS1 and RS2 cells, the latter encountered only in the infragranular layers. Synaptic responses were elicited by focal electrical stimuli in the ventrobasal nucleus of the thalamus (VB) while holding the cells at different membrane potentials. Postsynaptic potentials were classified as excitatory (EPSPs) or inhibitory (IPSPs), and their latencies were measured from the onset of the extracellularly recorded fiber volley in layer IV. EPSPs fell into three groups, according to latency. Those in the early cluster had latencies shorter than 1 msec and were coincident with the postsynaptic layer IV population response; they were considered monosynaptic. A second group, with latencies between 1.3 and 2.5 msec, were coincident with all IPSPs and were classified as disynaptic. The rest had latencies longer than 5 msec and were considered polysynaptic. The synaptic order of a cell was correlated with its laminar position and its electrophysiological class. Specifically, monosynaptic responses were restricted to infragranular RS cells and to FS cells, while disynaptic EPSPs were found in supragranular RS cells and in IB cells. Disynaptic IPSPs were found in both deep and superficial layers; in the deep layers they nearly always followed monosynaptic EPSPs, while in the superficial layers they were mostly found in isolation. We conclude that the intrinsic spiking characteristics of a neuron are an important determinant of its position in the cortical circuit and may have a substantial role in determining its response properties.

Action Potentials↗
PubMed1991

Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons.

Rhythmic activity in the neocortex varies with different behavioral and pathological states and in some cases may encode sensory information. However, the neural mechanisms of these oscillations are largely unknown. Many pyramidal neurons in layer 5 of the neocortex showed prolonged, 5- to 12-hertz rhythmic firing patterns at threshold. Rhythmic firing was due to intrinsic membrane properties, sodium conductances were essential for rhythmicity, and calcium-dependent conductances strongly modified rhythmicity. Isolated slices of neocortex generated epochs of 4- to 10-hertz synchronized activity when N-methyl-D-aspartate receptor-mediated channels were facilitated. Layer 5 was both necessary and sufficient to produce these synchronized oscillations. Thus, synaptic networks of intrinsically rhythmic neurons in layer 5 may generate or promote certain synchronized oscillations of the neocortex.

Animals↗
PubMed1991

Thalamocortical responses of mouse somatosensory (barrel) cortex in vitro.

We have developed a novel slice preparation of the mouse somatosensory forebrain. This preparation is unique in including both the ventrobasal nucleus of the thalamus and the sensorimotor "barrel" cortex in a 400-microns-thick slice with the functional connectivity between them preserved, and in allowing direct visualization of the various components of the barrel system in unstained living tissue. Thalamocortical connectivity was demonstrated by recording the laminar profile of cortical field potentials evoked electrically from the ventrobasal nucleus. Current-source density analysis of this profile showed that the largest and earliest sinks were coextensive with the two known sites of thalamocortical terminals, layer IV and the junction of layers V and VI. The sink in layer IV could be dissociated experimentally into a small, early sink of presynaptic origin (most probably a presynaptic spike volley in the thalamocortical terminals) and a later, larger sink generated postsynaptically. By mapping the subcortical stimulation sites that elicited a response at different layer IV recording sites we concluded that the thalamus-to-cortex projection preserves the general dorsoventral relationship of the afferents. Intracellularly recorded responses elicited by thalamic stimulation included (but were not limited to) monosynaptic excitatory and disynaptic inhibitory postsynaptic potentials. The thalamus-to-cortex connections were also mapped with the axonal fluorescent tracer dioctadecyl-tetramethylindocarbocyanine perchlorate. The thalamo-cortical slice is a very suitable system for studying the physiology and pharmacology of the thalamocortical synapse and for exploring the synaptic circuitry of the somatosensory cortex.

Animals↗
PubMed1991

Laminar distribution of neuronal membrane properties in neocortex of normal and reeler mouse.

1. Reeler is an autosomal recessive mutation of mice that alters neuronal migration during development, yielding a general inversion of the laminae in the neocortex. We recorded in vitro from slices of normal and reeler neocortex to study the influence of neuron position and shape on membrane properties and synaptic responses. 2. The intrinsic firing patterns, action-potential shapes, resting membrane potentials, input resistances, and evoked excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) did not differ between reelers and controls when data were grouped. 3. The depth distribution of intrinsic firing patterns was inverted in the reeler: intrinsically bursting (IB) neurons were found only in layer 5 in the normal mouse, but they were found exclusively in supragranular layers of the reeler cortex. 4. The spatial distribution of synaptic responses in the reeler was also inverted: very prominent IPSPs were characteristic of upper layer neurons in the normal mouse, but in the reeler similar inhibitory responses were observed predominantly in deep infragranular layers. 5. Dye injections in reeler pyramidal neurons revealed atypical morphologies, including distorted apical dendrites and cell inversion. 6. The data imply that cortical neurons develop the membrane and synaptic properties appropriate to their function, despite being malformed and mispositioned.

Animals↗
PubMed1990

Intrinsic firing patterns of diverse neocortical neurons.

Neurons of the neocortex differ dramatically in the patterns of action potentials they generate in response to current steps. Regular-spiking cells adapt strongly during maintained stimuli, whereas fast-spiking cells can sustain very high firing frequencies with little or no adaptation. Intrinsically bursting cells generate clusters of spikes (bursts), either singly or repetitively. These physiological distinctions have morphological correlates. RS and IB cells can be either pyramidal neurons or spiny stellate cells, and thus constitute the excitatory cells of the cortex. FS cells are smooth or sparsely spiny non-pyramidal cells, and are likely to be GABAergic inhibitory interneurons. The different firing properties of neurons in neocortex contribute significantly to its network behavior.

Animals↗