The auditory steady-state response is not a suitable monitor of anesthesia.

UNLABELLED: Previous studies show that the human 40-Hz auditory steady-state response (ASSR) disappears on induction of general anesthesia, suggesting that it may be a good candidate for a monitor of anesthesia. In this study, we aimed to learn whether all normal alert adults display ASSRs with adequate signal-to-noise ratio. Clicks were presented at a series of frequencies between 35 and 70 Hz and electroencephalographic records taken at the vertex were Fourier transformed. ASSRs were observable as sharp peaks in the electroencephalograph spectrum at the frequency of the clicks. Initial results showed that a discernible ASSR could not be obtained from about half the subjects studied at any click frequency used. Further investigation revealed that in subjects whose ASSR was undetectable in the alert state, induction of a drowsy mental state resulted in appearance of an observable ASSR. This was attributable to an increase in signal in the drowsy state, not to a decrease in noise. We conclude that, because a significant proportion of subjects do not display easily recordable ASSRs when alert, it is not practical to use disappearance of the ASSR as a routine test for adequacy of anesthesia. IMPLICATIONS: Auditory steady-state responses (ASSRs) are brain waves evoked by auditory stimuli. Because they reportedly disappear under general anesthesia, they have been suggested as potential indicators of anesthetic depth. However, in this study, we show that about half our normal adult subjects did not produce measurable ASSRs when awake. This suggests that ASSRs are not good candidates for use in monitoring anesthetic depth during surgery.

On subjective back-referral and how long it takes to become conscious of a stimulus: a reinterpretation of Libet's data.

The original data reported by Benjamin Libet and colleagues are reinterpreted, taking into account the facilitation which is experimentally demonstrated in the first of their series of articles. It is shown that the original data equally well or better support a quite different set of conclusions from those drawn by Libet. The new conclusions are that it takes only 80 ms (rather than 500 ms) for stimuli to come to consciousness and that "subjective back-referral of sensations in time" to the time of the stimulus does not occur (contrary to Libet's original interpretation of his results).

Anesthesia and the electrophysiology of auditory consciousness.

Empirical work is reviewed which correlates the presence or absence of various parts of the auditory evoked potential with the disappearance and reemergence of auditory sensation during induction of and recovery from anesthesia. As a result, the hypothesis is generated that the electrophysiological correlate of auditory sensation is whatever neural activity generates the middle latency waves of the auditory evoked potential. This activity occurs from 20 to 80 ms poststimulus in the primary and secondary areas of the auditory cortex. Evidence is presented suggesting that earlier or later waves in the auditory evoked potential do not covary with auditory sensation (as opposed to auditory perception) and it is therefore suggested that they are possibly not the electrophysiological correlates of sensation.

Membrane properties of deep dorsal horn neurons from neonatal rat spinal cord in vitro.

Whole-cell patch-clamp recordings were undertaken to characterize and compare the membrane properties of deep dorsal horn neurons in transverse slices of rat lumbar spinal cord in two age groups, postnatal days (P) 3-6 and 9-16. In both age groups, significant correlations were observed between membrane time constant and cell resistance and between action potential height and its duration at half-maximal amplitude. Cell resistance and action potential half-width values were lower in the P9-16 age group. Neurons were divided into four categories based on their firing properties in response to intracellular current injection: single spike, phasic firing, repetitive firing, and delayed firing. The distribution of neurons within these categories was similar in both age groups which suggests that the firing properties of deep dorsal horn neurons are functionally differentiated at an early postnatal age.

Primary afferent-evoked synaptic plasticity in deep dorsal horn neurons from neonatal rat spinal cord in vitro.

Whole-cell patch clamp recordings of deep dorsal horn neurons were undertaken in 'thick' transverse slices to demonstrate plasticity of primary afferent-evoked synaptic responses following conditioning stimulation. Synaptic plasticity was observed in neurons throughout the age range examined (postnatal days 3-6 and 9-16) but only long-term depression (LTD) was evocable in older animals (P9-16). Both short- and long-latency synaptic responses could undergo long-term potentiation (LTP) and LTD suggesting that AMPA/kainate and NMDA receptor-evoked responses are modifiable.

Long-term potentiation and depression in the intermediate gray matter of rat spinal cord in vitro.

Field potentials recorded from a group of cells in the intermediomedial gray matter of spinal cord slices from neonatal rats showed long-term potentiation and long-term depression in response to brief bursts of high frequency conditioning stimulation. Both N-methyl-D-aspartic acid-dependent and N-methyl-D-aspartic acid-independent long-term potentiation was seen. The long-term depression was partially reversed, but not prevented from occurring, by the opiate antagonist naloxone. The frequency of occurrence of long-term potentiation and depression was affected by the inhibitory blockers bicuculline and strychnine in a fashion consistent with the hypothesis that a slight depolarization favoured long-term potentiation and a larger depolarization favoured long-term depression.

Long-term potentiation and depression in the ventral horn of rat spinal cord in vitro.

The aim of this study was to see whether long-term potentiation (LTP) and/or long-term depression (LTD) of synaptic efficacy could be induced in the ventral horn of the rat spinal cord. Transverse slices were cut from neonatal rat spinal cords and maintained in vitro. Field potentials were recorded in the ventral horn in response to stimulation of the dorsal horn-intermediate nucleus region of the slice. Tetanic stimulation at 100 Hz (6 bursts of 50 pulses with 10 s between bursts) resulted in long-term potentiation in 25% of slices, long-term depression in 33% of slices and no long-lasting change of field potential amplitude in the rest. The long-term changes lasted at least 2.5 hours. The principal conclusion of the work is that LTP and LTD can be elicited in the ventral horn.

Cyclic AMP and long-term potentiation in the CA1 region of rat hippocampus.

Bath application of dibutyryl cyclic AMP, 8-bromo cyclic AMP or forskolin to hippocampal slices caused a short-lasting decrease, followed after washout by a long-lasting increase in the amplitude of population spikes recorded in area CA1 in response to 0.05 Hz stimulation of the Schaffer collateral/commissural pathway. Population spike depression lasted only as long as the cyclic AMP analogues were present in the bath, while the potentiation lasted for at least 2 h after they were washed out. Population excitatory postsynaptic potential amplitude was depressed while dibutyryl cyclic AMP was present in the bath, but after washout it was not significantly different from baseline amplitude. The population spike depression caused by dibutyryl cyclic AMP was prevented by the adenosine antagonist 8-p-sulfophenyltheophylline, but the long-lasting potentiation was not. Thus the transient depression induced by dibutyryl cyclic AMP was probably caused by an action of the drug or its breakdown products as adenosine agonists. The long-lasting potentiation is caused by a different mechanism. Occlusion experiments were performed to examine the relationship of the long-lasting population spike potentiation caused by dibutyryl cyclic AMP to the population spike long-term potentiation caused by high-frequency stimulation. High-frequency stimulation delivered after the population spike potentiation caused by dibutyryl cyclic AMP was established did cause a further potentiation, but only up to the level caused by high-frequency stimulation alone. Dibutyryl cyclic AMP administered after high frequency stimulation-induced long-term potentiation was established had no further potentiating effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic AMP induces long-term increase in synaptic efficacy in CA1 region of rat hippocampus.

The membrane permeable cyclic AMP analogue dibutyryl cAMP was found to have a biphasic effect on the amplitude of population spikes recorded in area CA1 of rat hippocampal slices in response to 0.05 Hz stimulation of the Schaffer collateral/commissural path. While dbcAMP was present the population spike was depressed and after washout of dbcAMP the population spike showed potentiation lasting at least 2 h. The population excitatory postsynaptic potential (EPSP) was unaffected. Addition of picrotoxin throughout the experiment caused no change in the depression but reduced the potentiation caused by dbcAMP. We conclude that cAMP may play a role in long-term potentiation (LTP).

Presynaptic activity in the period immediately after conditioning is not necessary for long-term potentiation.

The stratum radiatum of in vitro slices of rat hippocampus was tetanically stimulated to induce long-term potentiation (LTP) in CA1 neurons. One group of slices received test stimuli immediately after tetanisation, whilst another received no test stimuli until 30 min afterwards. No difference (P greater than 0.65) was found between the magnitude of LTP induced in the two groups of slices. This result demonstrates that the induction and maintenance of LTP does not require presynaptic release of transmitter or other neuroactive substances in the period immediately after tetanisation.

A chloride channel in excised patches from cultured rat hippocampal neurons.

A non-calcium-dependent chloride channel of conductance 62 pS, found in isolated inside-out patches of cultured fetal rat hippocampal neurons, is described. The channel does not require the presence of any neurotransmitter to be active and probably plays a part in maintaining the normal resting membrane potential.

Long-term depression at synapses in slices of rat hippocampus can be induced by bursts of postsynaptic activity.

In slices of rat hippocampus, a train of conditioning pulses that would produce long-term potentiation (LTP) if applied to afferent inputs was found to produce a long-lasting depression of Schaffer collateral/commissural synapses on CA1 cells when instead it was applied to the CA1 axons. The depression lasted undiminished for up to 2 h (the maximum duration of recording). Intracellular recording showed that long-term depression (LTD) of e.p.s.p. amplitude occurred in 66% of cells when this antidromic conditioning stimulation was delivered in normal medium, and in 100% of cells when the antidromic stimulation was delivered in medium containing sufficient Mg++ to block all synaptic transmission. We infer that the difference is because conditioning stimuli sometimes activated test synapses in normal Mg++ but could not in high Mg++. The fact that LTD could be induced in high Mg++ eliminates enhanced inhibitory feedback as a possible mechanism of the long lasting synaptic depression and demonstrates that the mechanism is probably postsynaptic. Resting membrane potential and cell input resistance were the same before and after conditioning, so persisting changes in these postsynaptic parameters can not be the explanation for LTD. LTD of the sort described in this paper could have significant implications for models of learning and memory.

Postsynaptic control of the induction of long-term changes in efficacy of transmission at neocortical synapses in slices of rat brain.

1. Long-term potentiation (LTP) is an enduring, activity-induced increase in the efficacy of synaptic transmission, which has been considered as a possible neural substrate for learning. Recent experiments have shown that LTP can be induced in hippocampal CA1 neurons when a presynaptic volley is paired repetitively with depolarization of the postsynaptic cell, brought about with intracellularly applied depolarizing current pulses (20, 33). We have repeated these experiments in neocortical neurons, in transverse slices of rat sensorimotor cortex in vitro. 2. Stable intracellular recordings were obtained from 28 neurons (mean resting potential -78 mV, mean spike amplitude 95 mV, mean input resistance 41 M omega) mostly in layers V and VI. Two different afferent pathways were stimulated alternately at 0.2 Hz to evoke subthreshold composite excitatory postsynaptic potentials (EPSPs). One micromolar bicuculline methiodide was added to the bathing medium in most experiments. 3. Repetitive pairing of one afferent volley with a coincident intracellular depolarizing current pulse (100-200 ms long) of a magnitude sufficient to make the neuron fire 6 to 13 action potentials/pulse, gave rise after 30-50 pairings in 4 neurons to a significant enduring increase in the amplitude of the paired EPSP. The increase persisted without decrement for as long as the recording continued (range 15-50 min after the pairing ended) but the amplitude of the unpaired EPSP was unchanged. During the LTP, the membrane potential and the apparent input resistance of the postsynaptic neurons were also unchanged. 4. In two cells a significant prolonged depression of the paired EPSP was induced while the unpaired EPSP was unaffected. Membrane potential and input resistance were not changed. In the remaining 22 cells neither the paired nor the unpaired EPSP was altered. 5. Brief, tetanic stimulation was applied to one afferent pathway in 11 of the neurons in which postsynaptic stimulation had been ineffective. A variety of effects was produced (LTP, depression, or posttetanic potentiation). All the effects of tetanic stimulation were confined to the stimulated pathway. 6. We conclude that LTP can be produced in some neocortical neurons by pairing a presynaptic volley with postsynaptic depolarization, in an experimental paradigm that conforms to Hebb's (17) model of associative conditioning. Depression of the paired EPSP was produced in other cells with the same experimental design.(ABSTRACT TRUNCATED AT 400 WORDS)

Control of number and distribution of synapses during ectopic synapse formation in adult rat soleus muscles.

Changes in the number and distribution of synaptic inputs and acetylcholine receptor clusters were studied during the formation of ectopic nerve-muscle junctions between the transplanted fibular nerve and the denervated soleus muscle of adult rats. The tibial nerve was cut 3 weeks after implanting the fibular nerve. New sites of transmission were first detected 3 days after the cut. These sites were located electrophysiologically, marked by dye and found to coincide with clusters of acetylcholine receptors. There were no ectopic clusters away from fibular nerve sprouts and no clusters on muscles which had not been denervated. Three days after cutting the tibial nerve, the acetylcholine receptor clusters, and probably also the sites of transmission, were randomly distributed along individual muscle fibres. Six days after the cut, the clusters continued to be randomly distributed whereas the synaptic inputs were either close together (within 300 microns) or more than 600 microns apart. Two weeks later the spatial distributions of both clusters and inputs were similar with peaks around 100-300 microns, 1200-1400 microns and 2000-2600 microns. No ectopic clusters were closer than 0.5 mm to the original endplate. We conclude that nerve-muscle contacts and associated acetylcholine receptor clusters initially form at random. One or a few of these contacts develop further and, as a result, the surrounding regions undergo changes that prevent the contacts initially formed there from being maintained. Apparently, in this preparation, approximately 1.5 mm length of fibre is needed to support the maturation and maintenance of each ectopic endplate (mean length 111 micron).

Problems with the use of the toe-spreading reflex in rats as an assay in nerve regeneration studies.

Stages in the return of the toe-spreading reflex after sciatic nerve injury were examined using the rat. It was found that the earliest stages in the return of the reflex do not indicate nerve regeneration, but rather reflect the development of adrenalin sensitivity in denervated muscles. Probably systemic adrenalin released during the reflex-testing procedure causes muscle contractions which imitate a nerve-induced toe-spread reflex.

Temperature dependence of neurotransmitter release in the antarctic fish Pagothenia borchgrevinki.

The quantal contents of endplate potentials from extraocular muscles of an antarctic fish Pagothenia borchgrevinki were measured over a range of temperatures. Quantal release was maximal at about 5 degrees C but showed little dependence on temperature between -2 degrees C and 10 degrees C. Above 10 degrees C quantal content declined until release ceased about 18 degrees C. In view of the fact that the ambient temperature at which these fish live is constant at -1.9 degrees C, the results suggest that Pagothenia borchgrevinki is only partially adapted to its environment despite 25 million years acclimatization.

Long-term potentiation and depression in hippocampal slices.

Antidromic stimulation of hippocampal CA 1 cells, in the presence of Mg2+ to eliminate synaptic transmission and with a pattern of impulses which when applied via a synaptic pathway produced long-term potentiation, was found to decrease the response of the CA 1 cells to subsequent synaptic activation. It was found that stimulation via synapses with the same pattern of stimuli caused long-term potentiation in normal conditions but not in the presence of 25 mM Mg2+.

Dopamine changes the shape of action potentials in hippocampal pyramidal cells.

Dopamine was found to have two electrophysiological effects on CA1 pyramidal cells in rat hippocampal slices. It increased the slow afterhyperpolarisation caused by a slow Ca2+-activated K+ conductance and it had an effect on action potentials that is postulated to be due to an increase in a fast Ca2+-activated K+ conductance. A given CA1 cell showed either one or both of the two responses to dopamine, or no response.

Acceleration of peripheral nerve regeneration after crush injury in rat.

It the sciatic nerve of a rat is crushed in the thigh, axons from the proximal side of the crush will regenerate so that the toe-spreading reflex becomes observable again after 10.4 +/- 1.7 (mean +/- S.D.) days. If the nerve is electrically stimulated for 0.25-1.0 h at the crush site, just after the crush occurs, the toe-spreading reflex first becomes observable 4.14 +/- 1.6 (mean +/- S.D.) days after the crush. Stimulation is most effective if delivered immediately after the crush but can be delayed up to an hour and still cause significantly faster regeneration. This phenomenon could be useful in clinical management of crushed peripheral nerves.