James R. Ison

Latency and amplitude changes in the acoustic startle reflex of the rat produced by variation in auditory prestimulation.

Two experiments investigated the effect of an auditory prestimulus (S1) on the amplitude and latency of the startle reflex to an intense tone burst (S2). In the first, with a fixed S1 intensity, with very short (<15 msec) ISIs reflex amplitudes were increased and latencies reduced by S1 presence and with longer intervals (⩾40 msec) amplitudes were reduced and latencies increased. Inhibition was apparent on the amplitude measure at lag times ineffective in altering the latency measure. In the second, with a fixed and long S1 duration reflex amplitudes increased with an increase in S1 intensity up to moderate (≈75 db) levels, but further increases in S1 produced a reduction in amplitudes. However any increase in S1 intensity over the minimum value tested (60 db) resulted in an increment in reflex latency. These experiments reveal the presence of three separable influences of auditory prestimuli on the acoustic startle reflex in the rat.

Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices

Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age‐related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age‐related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age‐related sensory loss. Together, our results suggest that the age‐related alteration of glial cells in sensory cortical areas can be accelerated by activity‐driven central mechanisms that result from an age‐related loss of peripheral sensitivity. In light of our observations, these age‐related changes in sensory function should be considered when investigating cellular, cortical, and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models.

Neural correlates of behavioral gap detection in the inferior colliculus of the young CBA mouse

Abstract The gap detection paradigm is frequently used in psychoacoustics to characterize the temporal acuity of the auditory system. Neural responses to silent gaps embedded in white-noise carriers, were obtained from mouse inferior colliculus (IC) neurons and the results compared to behavioral estimates of gap detection. Neural correlates of gap detection were obtained from 78 single neurons located in the central nucleus of the IC. Minimal gap thresholds (MGTs) were computed from single-unit gap functions and were found to be comparable, 1–2 ms, to the behavioral gap threshold (2 ms). There was no difference in MGTs for units in which both carrier intensities were collected. Single unit responses were classified based on temporal discharge patterns to steady-state noise bursts. Onset and primary-like units had the shortest mean MGTs (2.0 ms), followed by sustained units (4.0 ms) and phasic-off units (4.2 ms). The longest MGTs were obtained for inhibitory neurons (x¯ = 14 ms). Finally, the time-course of behavioral and neurophysiological gap functions were found to be in good agreement. The results of the present study indicate the neural code necessary for behavioral gap detection is present in the temporal discharge patterns of the majority of IC neurons.

Temporal resolution of gaps in noise by the rat is lost with functional decortication.

In Experiment 1 (n = 8), the rats ability to detect brief gaps in white noise was measured by gap-produced inhibition of an acoustic startle reflex, elicited 100 ms after the gap. After bilateral application of KCl to the cortex, gaps as long as 15 ms provided no reflex inhibition; in contrast, the inhibitory threshold was between 2 and 4 ms in the saline control condition. In Experiment 2 (n = 13), noise pulses of 40, 50, or 70 dB were presented 20-500 ms before the startle stimulus, and in Experiment 3 (n = 5) noise offsets occurred so that the startle stimulus was presented at the end of a 2-30-ms gap. Noise pulses and offsets both inhibited reflex expression equally in saline- and KCl-treated animals. Differences between the normal (saline) functions of noise offsets and gaps suggest additional sensory processing with the longer lead time. The loss of gap sensitivity after KCl application indicates that gap processing, unlike pulses and offsets, depends on cortical mechanisms.

Genetic differences in avoidance learning by Rattus norvegicus: escape/avoidance responding, sensitivity to electric shock, discrimination learning, and open-field behavior.

The behaviors of rats selectively bred for either good or poor shuttle box avoidance learning were studied. The results of Experiment 1 indicated that the phenotypic difference in avoidance learning is not associated with differences in speed of escape or avoidance responding. Differences between the lines in frequency of intertrial responses (ITRs), which appear during training but not during pretest, suggest that ITRs in animals of the low-avoidance (SLA) line are more suppressed by electric shock than in animals of the high-avoidance (SHA) line. This result suggests that SLA animals may be more emotionally responsive than SHA animals. Experiment 2 demonstrated that the animals of the two lines do not differ in absolute sensitivity to electric shock, and Experiment 3 showed that the poor performance of the SLA line is not due to an inability to learn. Experiment 3 also provided evidence which suggests that the poor avoidance learning by SLA animals is due to their emotional reactivity. Observations of open-field behavior in Experiment 4 are consistent with this hypothesis. The major consistent correlate of the phenotypic difference in avoidance learning is greater emotionality or emotional reactivity in SLA than in SHA animals.

Temporal acuity in auditory function in the rat: reflex inhibition by brief gaps in noise.

The acoustic startle reflex in the rat is inhibited if a relatively weak stimulus precedes the startle-eliciting tone burst. This research explored the effect of brief silent periods (gaps) in white noise on the startle reflex, in order to describe the limits of temporal resolution in the auditory system of the rat. Brief silent periods did depress reflex behavior, and two responsible processes were identified. One was most evident at a 190-msec lead time between gap and startle tone. It yielded a linear decrement in reflex expression over a dynamic range of 0-7 msec, and an estimate for the threshold of temporal acuity of 3.5 msec. The second was evident primarily at a 40-msec interstimulus interval and had a linear effect over a dynamic range of at least 40 msec. Very brief gaps had a greater inhibitory effect at the 190-msec interval between gap and startle stimulus; prolonged gaps had their greater effect at the 40-msec interval. The first process was identified as reflex inhibition, which is sensitive to the sensory properties of the lead stimulus. The second process was identified as sensory adaptation, produced by noise exposure but unmasked by silence.

Facilitation and inhibition of the human startle blink reflexes by stimulus anticipation

The cutaneous eyeblink has 2 electromyographic components, 1 unilateral and early (R1) and 1 bilateral and late (R2), which are served by different neural pathways. These 2 reactions were measured when the eliciting stimulus was expected or relatively surprising. Forewarning was varied in 3 ways: Subjects received notice that the stimulus was about to occur on some trials (Experiment 1); delivered the stimulus to themselves on some trials (Experiments 2 & 3); or experienced a series of trials in which a tone was paired with the eliciting stimulus, followed by tone-alone trials interspersed with test trials (Experiment 4). In each case, forewarning enhanced R1 amplitudes while depressing R2 but reduced the latency of both components. This mixed pattern of effects reveals that the preparatory state provoked by forewarning focuses excitatory and inhibitory processes simultaneously on different reflex pathways: inhibition central and excitation peripheral.

Amobarbital sodium and instrumental performance changes following reward reduction

Amobarbital sodium eliminated the depression effect and rapid performance decrement found in normal animals after a reduction in reward. The rapid decline is generally attributed to a rapid shift in incentive motivation but these data indicate that it is dependent on the aversive consequences of conditioned emotional responses.

Behavioral and neural measures of auditory temporal acuity in aging humans and mice.

Three experiments compared auditory temporal acuity in humans and in the behavior and single cells in the inferior colliculus (IC) of mice, to establish the comparability of aging effects on temporal acuity across species, and to suggest a neural foundation. The thresholds for silent gaps placed in white noise (MGTs) were similar in young mice and young humans, and increased in some but not all old humans and old mice. Neural MGT in the most sensitive cells of both young and old mice was comparable to behavioral MGT in the young of both species, but older mice had more cells with very high MGT. Human listeners were selected to have minimal absolute hearing loss. Older mice had significant hearing loss that was correlated with MGT in behavioral, but not in neural, measures. Some old mice and some old IC cells, however, had low MGTs coupled with elevated absolute hearing thresholds. Age-related changes in temporal acuity appear comparable in humans and mice. The data suggest a common deficit in neural mechanisms.

Conditioning auditory stimuli and the cutaneous eyeblink reflex in humans: Differential effects according to oligosynaptic or polysynaptic central pathways

Electromyographic activity of orbicularis oculi muscles in humans was elicited by percutaneous electrical stimulation of the supraorbital brahcn of the trigeminal nerve. The reflex consists of an early brief ipsilateral R1 and a later prolonged consensual R2. The threshold for R1 was considerably elevated compared to that of R2. In one experiment brief acoustic stimuli, at 70 dB SPL, were presented at various intervals, from 5 to 800 msec, prior to the eliciting stimulus. In a second experiment similar stimuli, with intensities varying from 30 to 70 dB SPL, were given at the fixed lead time of 100 msec. In each experiment the preliminary acoustic stimulus enhanced R1 and depressed R2. Potentiation of R1 developed more rapidly than did depression of R2 and exhibited an early and a late peak, whereas depression had a single intermediate trough. Both effects linearly increased with increases in the intensity of the acoustic prepulse. These restuls are discussed in relation to the neuronal circuits responsible for the expression of the two reflex components.