The effect of state on sensory gating: comparison of waking, REM and non-REM sleep.

OBJECTIVES: Auditory sensory gating is an electrophysiological assay that has been employed in clinical and basic research to clarify the neurobiological basis of perceptual and attentional impairments associated with schizophrenia and other diseases. In addition to genetically-linked characteristics, this measure also exhibits potentially confounding sensitivity to behavioral state, most notably acute stress. The goal of the present study is to determine if auditory sensory gating of evoked potential component P50 ('P1') could be measured during rapid eye movement (REM) sleep, as an alternative to the waking state. METHODS: The suppression of vertex-recorded auditory evoked potential components, P30, P50 and N100, was measured as a function of stimulus redundancy using the paired-click paradigm during all-night sleep in 10 control subjects. Average evoked responses were computed separately for 30 min periods of waking, REM sleep, and non-REM (stage 2) sleep. RESULTS: Evoked response component P50 exhibited suppression to the paired-click stimulus during REM sleep, not significantly different than waking. Suppression of wave N100 was significantly poorer during both sleep stages than waking. Component P30 was not suppressed in response to repetitive stimuli under any state of vigilance. CONCLUSIONS: In addition to waking, response suppression of evoked potential component P50 can be measured during REM sleep, thus allowing the separation of trait- and state-dependent effects in future investigations of auditory sensory gating.

Daily variation and appetitive conditioning-induced plasticity of auditory cortex receptive fields.

Long-term modification of cortical receptive field maps follows learning of sensory discriminations and conditioned associations. In the process of determining whether appetitive - as opposed to aversive - conditioning is effective in causing such plastic changes, it was discovered that multineuron receptive fields, when measured in rats under ketamine-sedation, vary substantially over the course of a week, even in the absence of classical conditioning and electrode movement. Specifically, a simple correlation analysis showed that iso-intensity frequency response curves of multiunit clusters and local field potentials recorded from auditory cortex are nonstationary over 7 days. Nevertheless, significant plastic changes in receptive fields, due to conditioned pairing of a pure tone and electrical stimulation of brain reward centres, are detectable above and beyond these spontaneous daily variations. This finding is based on a novel statistical plasticity criterion which compares receptive fields recorded for three days before and three days after conditioning. Based on a more traditional criterion (i.e. one day before and after conditioning), the prevalence of learning-induced changes caused by appetitive conditioning appears to be comparable to that described in previous studies involving aversive conditioning.

Trial-to-trial variability and state-dependent modulation of auditory-evoked responses in cortex.

Recent experimental work has provided evidence that trial-to-trial variability of sensory-evoked responses in cortex can be explained as a linear superposition of random ongoing background activity and a stationary response. While studying single trial variability and state-dependent modulation of evoked responses in auditory cortex of ketamine/xylazine-anesthetized rats, we have observed an apparent violation of this model. Local field potential and unit spike trains were recorded and analyzed during different anesthesia depths-deep, medium, and light-which were defined by the pattern of ongoing cortical activity. Estimation of single trial evoked response was achieved by considering whole waveforms, rather than just one or two peak values from each wave. Principal components analysis was used to quantitatively classify waveforms on the basis of their time courses (i.e., shapes). We found that not only average response but also response variability is modulated by depth of anesthesia. Trial-to-trial variability is highest under medium levels of anesthesia, during which ongoing cortical activity exhibits rhythmic population bursting activity. By triggering the occurrence of stimuli from the spontaneously occurring burst events, we show that the observed variability can be accounted for by the background activity. In particular, the ongoing activity was found to modulate both amplitude and shape (including latency) of evoked local field potentials and evoked unit activity in a manner not predicted by linear superposition of background activity and a stereotyped evoked response. This breakdown of the linear model is likely attributable to rapid transitions between different levels of thalamocortical excitability (e.g., spike-wave discharges), although brain "state" is relatively fixed.

The continuum of operating modes for a passive model neuron.

Whether cortical neurons act as coincidence detectors or temporal integrators has implications for the way in which the cortex encodes information--by average firing rate or by precise timing of action potentials. In this study, we examine temporal coding by a simple passive-membrane model neuron responding to a full spectrum of multisynaptic input patterns, from highly coincident to temporally dispersed. The temporal precision of the model's action potentials varies continuously along the spectrum, depends very little on the number of synaptic inputs, and is shown to be tightly correlated with the mean slope of the membrane potential preceding the output spikes. These results are shown to be largely independent of the size of postsynaptic potentials, of random background synaptic activity, and of shape of the correlated multisynaptic input pattern. An experimental test involving membrane potential slope is suggested to help determine the basic operating mode of an observed cortical neuron.

Characterization, scaling, and partial representation of neural junctions and coordinated firing patterns by dynamic similarity.

This paper presents a dynamic-similarity-based system for mathematically characterizing the functional connectivity and information flow of neural junctions. This approach allows for quantitative comparison of operations of neural junctions across systems, and an interpretation of their connectivity parameters in terms of the flow of multiunit firing patterns. The paper further uses this characterization to show how to rationally construct reduced operational models of neural junctions. Both uniformly proportional scaling and partial fragmentary representations are developed. The uniformly scaled models are better adapted to overall capacities and broader theoretical conceptualizations; the partial representations are better adapted to direct comparison with microelectrode experimentation. The characterization of information flow is based on coordinated multiunit patterns such as synfire chains or sequential configurations. The system can be applied to component parts of large composite networks including junctions with topographical patchiness and other irregularities. The characterization should be of use to anatomists, physiologists, modelers, and theorists. The theory predicts that the necessity for cooperative confluence of synaptic potentials in sending and receiving sequential configurations across topographically constrained projection fields requires the existence of functional 'pattern modules' within the topographical synaptology of the junction.

Characterization, scaling, and partial representation of diffuse and discrete input junctions to CA3 hippocampus.

This paper applies a general mathematical system for characterizing and scaling functional connectivity and information flow across the diffuse (EC) and discrete (DG) input junctions to the CA3 hippocampus. Both gross connectivity and coordinated multiunit informational firing patterns are quantitatively characterized in terms of 32 defining parameters interrelated by 17 equations, and then scaled down according to rules for uniformly proportional scaling and for partial representation. The diffuse EC-CA3 junction is shown to be uniformly scalable with realistic representation of both essential spatiotemporal cooperativity and coordinated firing patterns down to populations of a few hundred neurons. Scaling of the discrete DG-CA3 junction can be effected with a two-step process, which necessarily deviates from uniform proportionality but nonetheless produces a valuable and readily interpretable reduced model, also utilizing a few hundred neurons in the receiving population. Partial representation produces a reduced model of only a portion of the full network where each model neuron corresponds directly to a biological neuron. The mathematical analysis illustrated here shows that although omissions and distortions are inescapable in such an application, satisfactorily complete and accurate models the size of pattern modules are possible. Finally, the mathematical characterization of these junctions generates a theory which sees the DG as a definer of the fine structure of embedded traces in the hippocampus and entire coordinated patterns of sequences of 14-cell links in CA3 as triggered by the firing of sequences of individual neurons in DG.

Yohimbine impairs P50 auditory sensory gating in normal subjects.

The evoked response to repeated auditory stimuli generally decreases in amplitude, a phenomenon that demonstrates the activity of sensory gating mechanisms in the central nervous system (CNS). Gating of the P50 wave of the auditory evoked response shows such behavior in normals, but not in schizophrenic or manic subjects. In mania, diminished gating of the auditory evoked response is correlated with elevated levels of noradrenergic metabolites. In animals, yohimbine, a presynaptic alpha-2 antagonist, increases noradrenergic neuronal transmission in the CNS and diminished gating of the auditory evoked response. The aim of this experiment was to test whether yohimbine causes diminished auditory sensory gating in normal human controls. Seven normal subjects with normal P50 auditory gating were treated either with 0.4 mg/kg of oral yohimbine on one day or placebo on a different day. Each subject acted as his own control. Yohimbine, but not placebo, caused a significant but transient decrease in P50 auditory gating in these subjects. Thus, increasing CNS noradrenergic neuronal transmission in normal controls can cause a transient impairment in auditory sensory gating.