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B W Connors

Publications and source records attributed to B W Connors.

64 records · Page 4Linked to original sources
PubMed1982

Rat optic nerve: electrophysiological, pharmacological and anatomical studies during development.

Changes in conduction properties and in morphology were studied during rat optic nerve growth from birth (when no myelin is present and the glia have not differentiated) to adulthood (when the optic nerve is essentially 100% myelinated). Myelination begins around the sixth postnatal day and proceeds rapidly so that 85% of the fibers are myelinated at 28 days of age. Mean diameter of optic nerve axons remains about 0.2 micron for the first week and then increases rapidly if the fiber is being myelinated. Those axons not being myelinated remain about 0.2-0.3 micron in diameter. At birth the compound action potential has a single negative peak and a conduction velocity of about 0.2 m/s. The increase in conduction velocity prior to myelination is considerably greater than can be accounted for on the basis of increase in axonal diameter. There is no clear step increase in the velocity of the shortest latency peak correlated with the onset of myelination. During myelination the compound action potential develops multiple short latency components, which evolve into the adult-like 3 component compound action potential by 3-4 weeks of age. Durations of the relative refractory period and supernormal period decrease as age increases, but are not related to myelination in a simple manner. Sodium appears to be the only significant carrier of inward current at all ages. A measureable calcium conductance is not present at any age. Voltage-dependent potassium conductance contributes to the compound action potential at all ages, but the response to 4-aminopyridine in rapidly conducting fibers is apparently smaller than that in slowly conducting fibers. These results show that conduction can occur before myelination or the differentiation of glial cells. Moreover, changes in conduction velocity do not depend entirely on myelination or increases in axonal size. Finally, these results suggest a reorganization of axonal membrane properties during the development of rat optic nerve.

Animals↗
PubMed1982

Electrophysiological properties of neocortical neurons in vitro.

1. Intracellular recordings were obtained from neurons of the guinea pig sensorimotor cortical slice maintained in vitro. Under control recording conditions input resistances, time constants, and spiking characteristics of slice neurons were well within the ranges reported by other investigators for neocortical neurons in situ. However, resting potentials (mean of -75 mV) and spike amplitudes (mean of 93.5 mV) were 10-25 mV greater than has been observed in intact preparations. 2. Current-voltage relationships obtained under current clamp revealed a spectrum of membrane-rectifying properties at potentials that were subthreshold for spike generation. Ionic and pharmacologic analyses suggest that subthreshold membrane behavior is dominated by voltage-sensitive, very slowly inactivating conductances to K+ and Na+. 3. Action potentials were predominantly Na+ dependent under normal conditions but when outward K+ currents were reduced pharmacologically, it was possible, in most cells, to evoke a non-Na+-dependent, tetrodotoxin-(TTX) insensitive spike, which was followed by a prominent depolarizing after-potential. Both of these events were blocked by the Ca2+ current antagonists, Co2+ and Mn2+. 4. A small population of neurons generated intrinsic, all-or-none burst potentials when depolarized with current pulses or by synaptic activation. These cells were located at a narrow range of depths comprising layer IV and the more superficial parts of layer V. 5. Spontaneous excitatory synaptic potentials appeared in all neurons. Spontaneous inhibitory events were visible in only about 10% of the cells, and in those cases apparently reversed polarity at a level slightly positive to resting potential. Stimulation of the surface of the slice at low intensities evoked robust and usually concurrent excitatory and inhibitory synaptic potentials. Unitary inhibitory postsynaptic potentials (IPSPs) reversed at levels positive to rest. Stronger stimulation produced a labile, long-duration, hyperpolarizing IPSP with a reversal potential 15-20 mV negative to the resting level. 6. Neocortical neurons in vitro retain the basic membrane and synaptic properties ascribed to them in situ. However, the array of passive and active membrane behavior observed in the slice suggests that cortical neurons may be differentiated by specific functional properties as well as by their extensive morphological diversity.

Action Potentials↗
PubMed1982

Mechanisms of neocortical epileptogenesis in vitro.

1. The cellular mechanisms underlying interictal epileptogenesis have been examined in an in vitro slice preparation of guinea pig neocortex. Penicillin or bicuculline was applied to the tissue, and intracellular recordings were obtained from neurons and glia. 2. Following convulsant application, stimulation could elicit a short-latency excitatory postsynaptic potential (EPSP) and a large, longer latency depolarization shift (DS) in single neurons. DSs in neurons of the slice were very similar to those evoked in neurons of neocortex in vivo in that they displayed an all-or-none character, large shifts in latency during repetitive stimuli, long afterpotentials, and a prolonged refractory period. In contrast to epileptogenesis produced by penicillin in intact cortex, neither spontaneous DSs nor ictal episodes were observed in neocortical slices. 3. In simultaneous recordings from pairs of neurons within the same cortical column, DS generation and latency shifts were invariably synchronous. DS generation in neurons was also coincident with large, paroxysmal increases of extracellular [K+], as indicated by simultaneous recordings from glia. 4. When polarizing currents were applied to neurons injected with the local anesthetic QX-314, the DS amplitude varied monotonically and had an extrapolated reversal potential near 0 mV. In neurons injected with the K+-current blocker Cs+, large displacements of membrane potential were possible, and both the short-latency EPSP and the peak of the DS diminished completely at about 0 mV. At potentials positive to this, the short-latency EPSP was reversed, and the DS was replaced by a paroxysmal hyperpolarization whose rise time and peak latency were prolonged compared to the DS evoked at resting potential. The paroxysmal hyperpolarization probably represents the prolonged activation of the impaled neuron by EPSPs. 5. Voltage-dependent components, including slow spikes, appeared to contribute to generation of the DS at resting potential in Cs+-filled cells, and these components were blocked during large depolarizations. 6. The results suggest that DS generation in single neocortical neurons occurs during synchronous synaptic activation of a large group of cells. DS onset in a given neuron is determined by the timing of a variable-latency excitatory input that differs from the short-latency EPSP. The DS slow envelope appears to be generated by long-duration excitatory synaptic currents and may be modulated by intrinsic voltage-dependent membrane conductances. 7. We present a hypothesis for the initiation of the DS, based on the anatomical and physiological organization of the intrinsic neocortical circuits.

Animals↗
PubMed1982

Effects of local anesthetic QX-314 on the membrane properties of hippocampal pyramidal neurons.

The quaternary lidocaine derivative QX-314 was applied internally to CA1 pyramidal neurons of the guinea-pig hippocampal slice preparation. This local anesthetic blocked both fast, Na+-dependent action potentials and the voltage-dependent, non-inactivating Na+ conductance. Partially blocked Na+ spikes exhibited pronounced frequency-dependent depression at rates as low as 0.2 Hz. Ca++-dependent electrogenesis, synaptic potentials and glutamate-induced depolarizations were apparently unaffected even after large doses of QX-314. The results indicate that the cellular mechanisms of local anesthetics on central neuronal membranes are similar to those described for peripheral axons. The frequency-dependence of spike blockade may account for some of the effects of local anesthetics on the central nervous system in vivo. Additionally, the localized intracellular application of QX-314 may prove useful as a specific pharmacological tool in studies of central neurons.

Action Potentials↗
PubMed1981

Dye-coupling between glial cells in the guinea pig neocortical slice.

Physiologically identified glial cells in guinea pig neocortical slices were injected with the low molecular weight, fluorescent dye Lucifer yellow CH. The stained aggregates which resulted consisted of one brightly stained, central cell surrounded by numerous lightly stained cells. The central cell had well defined feathery processes and resembled a protoplasmic astrocyte. The surrounding cells appeared also to be glial cells but lacked sufficient detail to be further categorized. This first demonstration of dye-coupling between neocortical glial cells strongly suggests that these cells are connected together via low resistance junctions capable of passing ionic current as well as dye.

Animals↗
PubMed1981

A comparison of the effects of pentobarbital and diphenylhydantoin on the GABA sensitivity and excitability of adult sensory ganglion cells.

The actions of pentobarbital (PB) and diphenylhydantoin (DPH) have been studied on neurons of dorsal root ganglia from adult rats. At anesthetic level (i.e. 1--2 x 10(-4) M), PB greatly enhanced neuronal responses to gamma-aminobutyric acid (GABA); at 10(-3) M PB caused a small depolarization and profoundly attenuated GABA responses, probably because of cross-desensitization of GABA receptors. In contrast to results in some non-mammalian species, DPH (up to 2 x 10(-4) M) did not affect GABA responses under any conditions. PB depressed single intracellularly evoked action potentials only at high concentrations, but the cell's ability to fire trains of impulses in response to prolonged depolarization was impaired (i.e. accommodation was enhanced) at the anesthetic dosage level. DPH (1--2 x 10(-4) M) selectively depressed sodium-dependent action potentials of tetrodotoxin (TTX)-sensitive cells, and also impaired their ability to fire repetitively, but it did not influence sodium conductances and other aspects of excitability of TTX-insensitive neurons. In addition, both DPH and TTX reversed neuronal depolarizations induced by veratridine. Calcium-dependent potentials appeared to be unaltered by DPH. The results suggest that the anesthetic properties of PB may depend, in part, upon the enhancement of GABA-mediated inhibitions and increased accommodation. The anticonvulsant DPH exerts a selective, TTX-like depression of sodium conductances which does not extend to sodium conductances which are insensitive to TTX.

Animals↗
PubMedDate not supplied

Initiation of synchronized neuronal bursting in neocortex.

Epilepsy is characterized by highly synchronized paroxysmal bursts of activity within a large population of cortical neurones. Because such spontaneous, synchronized discharges can occur even in isolated blocks of neocortex, mechanisms for initiating and coordinating this activity must reside within the cortex itself. However, the specific cellular properties and local neural circuitry responsible for such behaviour are unknown. In a previous study of neocortex in vitro, we found that treatment with the convulsants penicillin and bicuculline led to synchronized bursts which were driven by unusually large and long-lasting excitatory synaptic conductances. I now report evidence that synchronized bursts are initiated by a small, spacially discrete subpopulation of cells located in the area comprising layer IV and upper layer V. Neural elements in these layers appear to project paroxysmal synaptic excitation radially, onto the neurones of other layers.

Animals↗
PubMedDate not supplied

Regenerative activity in apical dendrites of pyramidal cells in neocortex.

In intracellular recordings from three neocortical pyramidal cells in vitro, intracellular dye injection identified the impalement site as the primary trunk of the apical dendrite. Dendritic recordings displayed two types of regenerative events: relatively fast, low-threshold spikes with amplitudes of 12-69 mV, and slower, higher-threshold spikes up to 80 mV in amplitude. This distinctive dendritic firing pattern was also encountered in six recordings without dye-filled electrodes. Fast spike frequency was extremely sensitive to small changes in membrane potential at the recording site. In one recording, the fast spikes were blocked by 1 microM TTX, while slow events were spared. A computational model of a pyramidal cell was constructed to assist in interpreting the recordings. Simulations suggested that the fast spikes were generated primarily by active Na+ conductance concentrated at a distance from the impalement site, probably in the region of the soma. The low threshold of the fast spikes suggested that Na+ channels also exist in the apical dendrites, where they have a relatively low density. The data strongly imply that there are Ca2+ channels in the apical dendrites.

Action Potentials↗
PubMedDate not supplied

Properties of excitatory synaptic events in neurons of primary somatosensory cortex of neonatal rats.

We have characterized the development of synaptic responses from neurons of rat parietal cortex. Whole-cell recording was used in slice preparations in vitro. Neurons were stained with biocytin to allow their identification, and the sample included pyramidal neurons and Cajal-Retzius cells. Dye-coupling of 3-12 cells was frequently observed from the day of birth (P0) to P3. On average, when recorded with Cs(+)-filled electrodes, the input resistances of neonatal cells were large (mean = 1.1 G omega) and resting membrane potentials were relatively depolarized (mean = -45 mV) when compared to mature neocortical neurons. The application of an NMDA receptor antagonist usually hyperpolarized cells by 5-10 mV and increased their input resistance (mean increase = 83%), suggesting that immature neurons are tonically activated by excitatory amino acids (EAA) in our preparation. Excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) could be obtained from animals as young as P0 by brief stimulation of the subplate. Synaptic responses at these early ages had long durations, often lasting over hundreds of milliseconds, they reversed polarity around 0 mV, and they were blocked by tetrodotoxin and EAA antagonists. Pharmacology and current-voltage relationships demonstrated the presence of both NMDA receptor- and non-NMDA receptor-dependent components in most EPSPs. Unlike synaptic responses of mature neurons, neonatal synaptic responses were composed largely of NMDA receptor-dependent components. We did not observe inhibitory synaptic inputs before P6. In some neurons, single shocks to the subplate region initiated spontaneous EPSPs that lasted > 1 min. This study clearly demonstrates functional synapses in the neocortex of rats on the day of birth. Large NMDA receptor-mediated EPSPs with long duration could have a major influence on the development of cortical circuits in the neonate.

6-Cyano-7-nitroquinoxaline-2,3-dione↗