Electrophysiology publications

Sleep is a poorly understood behavior that predominates during infancy but is studied almost exclusively in adults. One perceived impediment to investigations of sleep early in ontogeny is the absence of state-dependent neocortical activity. Nonetheless, in infant rats, sleep is reliably characterized by the presence of tonic (i.e., muscle atonia) and phasic (i.e., myoclonic twitching) components; the neural circuitry underlying these components, however, is unknown. Recently, we described a medullary inhibitory area (MIA) in week-old rats that is necessary but not sufficient for the normal expression of atonia. Here we report that the infant MIA receives projections from areas containing neurons that exhibit state-dependent activity. Specifically, neurons within these areas, including the subcoeruleus (SubLC), pontis oralis (PO), and dorsolateral pontine tegmentum (DLPT), exhibit discharge profiles that suggest causal roles in the modulation of muscle tone and the production of myoclonic twitches. Indeed, lesions in the SubLC and PO decreased the expression of muscle atonia without affecting twitching (resulting in "REM sleep without atonia"), whereas lesions of the DLPT increased the expression of atonia while decreasing the amount of twitching. Thus, the neural substrates of infant sleep are strikingly similar to those of adults, a surprising finding in light of theories that discount the contribution of supraspinal neural elements to sleep before the onset of state-dependent neocortical activity.

Neurons in the adult visual cortex are capable of integrating signals over a large area that surrounds their classic receptive field (RF), and this ability of cortical neurons is thought to be intimately involved in perceptual binding. It is not known, however, at what age these long-range signal interactions emerge. Here, we report that qualitatively adult-like center/surround interactions are already present in the primary visual cortex as early as postnatal day 14 in macaque monkeys. However, the RF surrounds of visual area 2 (V2) neurons were largely absent until 4 weeks of age and, as late as 8 weeks of age, center/surround signal interactions in V2 neurons were immature. Our results suggest that the cortical circuits underlying the RF center/surround of individual neurons mature considerably later in V2 than in the primary visual cortex and give critical evidence for the hypothesis that the functional maturation of the primate visual brain proceeds in a hierarchical manner.

Spike-frequency adaptation is a prominent feature of many neurons. However, little is known about its computational role in processing behaviorally relevant natural stimuli beyond filtering out slow changes in stimulus intensity. Here, we present a more complex example in which we demonstrate how spike-frequency adaptation plays a key role in separating transient signals from slower oscillatory signals. We recorded in vivo from very rapidly adapting electroreceptor afferents of the weakly electric fish Apteronotus leptorhynchus . The firing-frequency response of electroreceptors to fast communication stimuli (“small chirps”) is strongly enhanced compared with the response to slower oscillations (“beats”) arising from interactions of same-sex conspecifics. We are able to accurately predict the electroreceptor afferent response to chirps and beats, using a recently proposed general model for spike-frequency adaptation. The parameters of the model are determined for each neuron individually from the responses to step stimuli. We conclude that the dynamics of the rapid spike-frequency adaptation is sufficient to explain the data. Analysis of additional data from step responses demonstrates that spike-frequency adaptation acts subtractively rather than divisively as expected from depressing synapses. Therefore, the adaptation dynamics is linear and creates a high-pass filter with a cutoff frequency of 23 Hz that separates fast signals from slower changes in input. A similar critical frequency is seen in behavioral data on the probability of a fish emitting chirps as a function of beat frequency. These results demonstrate how spike-frequency adaptation in general can facilitate extraction of signals of different time scales, specifically high-frequency signals embedded in slower oscillations.

Our current knowledge on sound detection in fishes is mainly based on data acquired under quiet laboratory conditions. However, it is important to relate auditory thresholds to background noise in order to determine the signal-detecting abilities of animals in the natural environment. We investigated the influence of two noise levels within the naturally occurring range on the auditory sensitivity of two hearing specialists (otophysines) and a hearing generalist. Audiograms of the goldfish Carassius auratus, the lined Raphael catfish Platydoras costatus and the pumpkinseed sunfish Lepomis gibbosus (hearing generalist) were determined between 200 and 4000 Hz (100-800 Hz for L. gibbosus) under laboratory conditions and under continuous white noise by recording auditory evoked potentials (AEPs). Baseline thresholds showed greatest hearing sensitivity around 500 Hz in goldfish and catfish and at 100 Hz in the sunfish. Continuous white noise of 110 dB RMS elevated the thresholds by 15-20 dB in C. auratus and by 4-22 dB in P. costatus. White noise of 130 dB RMS elevated overall hearing thresholds significantly in the otophysines by 23-44 dB. In the goldfish, threshold did not shift at 4 kHz. In contrast, auditory thresholds in the sunfish declined only at the higher noise level by 7-11 dB. Our data show that the AEP recording technique is suitable for studying masking in fishes, and that the occurrence and degree of the threshold shift (masking) depend on the hearing sensitivity of fishes, the frequency, and noise levels tested. The results indicate that acoustic communication and orientation of fishes, in particular of hearing specialists, are limited by noise regimes in their environment.

Humans and animals detect low-level tones masked by slowly fluctuating noise very efficiently. A possible neuronal correlate of this phenomenon is the ability of low-level tones to suppress neuronal locking to the envelope of the fluctuating noise (“locking suppression”). Using in vivo intracellular and extracellular recordings in cats, we studied neuronal responses to combinations of fluctuating noise and tones in three successive auditory stations: inferior colliculus (IC), medial geniculate body (MGB), and primary auditory cortex (A1). We found that although the most sensitive responses in the IC were approximately isomorphic to the physical structure of the sounds, with only a small perturbation in the responses to the fluctuating noise after the addition of low-level tones, some neurons in the MGB and all A1 neurons displayed striking suppressive effects. These neurons were hypersensitive, showing suppression already with tone levels lower than the threshold of the neurons in silence. The hypersensitive locking suppression in A1 and MGB had a special timing structure, starting >75 ms after tone onset. Our findings show a qualitative change in the representation of tone in fluctuating noise along the IC-MGB-A1 axis, suggesting the gradual segregation of signal from noise and the representation of the signal as a separate perceptual object in A1.

Compared with auditory nerve (AN) fibers, trapezoid body (TB) fibers of the cat show enhanced synchronization to low-frequency tones. This phenomenon probably contributes to the high temporal resolution of binaural processing. We examined whether enhanced synchronization also occurs to sustained broadband noise. We recorded responses to a reference Gaussian noise and its polarity-inverted version in the TB of barbiturate-anesthetized cats. From these we constructed shuffled autocorrelograms (SACs) and quantified spike timing by measuring the amplitude and width of their central peak. Many TB fibers with low characteristic frequency (CF) showed SACs with higher and narrower central peaks than ever observed in the AN, indicating better consistency and precision of temporal coding. Larger peaks were also observed in TB fibers with high CF, but this was mostly caused by higher average firing rates, resulting in a larger number of coincident spikes across stimulus repetitions. The results document monaural preprocessing of the temporal information delivered to binaural nuclei in the olivary complex, which likely contributes to the high sensitivity to interaural time differences.

Neurons in primary auditory cortex (A1) of cats show strong stimulus-specific adaptation (SSA). In probabilistic settings, in which one stimulus is common and another is rare, responses to common sounds adapt more strongly than responses to rare sounds. This SSA could be a correlate of auditory sensory memory at the level of single A1 neurons. Here we studied adaptation in A1 neurons, using three different probabilistic designs. We showed that SSA has several time scales concurrently, spanning many orders of magnitude, from hundreds of milliseconds to tens of seconds. Similar time scales are known for the auditory memory span of humans, as measured both psychophysically and using evoked potentials. A simple model, with linear dependence on both short-term and long-term stimulus history, provided a good fit to A1 responses. Auditory thalamus neurons did not show SSA, and their responses were poorly fitted by the same model. In addition, SSA increased the proportion of failures in the responses of A1 neurons to the adapting stimulus. Finally, SSA caused a bias in the neuronal responses to unbiased stimuli, enhancing the responses to eccentric stimuli. Therefore, we propose that a major function of SSA in A1 neurons is to encode auditory sensory memory on multiple time scales. This SSA might play a role in stream segregation and in binding of auditory objects over many time scales, a property that is crucial for processing of natural auditory scenes in cats and of speech and music in humans.

The jamming avoidance response of the weakly electric fish Gymnarchus niloticus relies on determining the sign of the frequency difference (Df) between the fish's own electric organ discharge (EOD) and that of a neighbor, which is achieved by comparing modulations in amplitude (AM) and phase (PM) that result from the summation of their EODs. These two stimulus features are processed in separate pathways that converge in the torus semicircularis on combination-sensitive neurons, many of which are selective for the sign of Df. We recorded extracellular single-unit responses to independent stimulation with AM and PM and combined AM-PM stimulation to determine how sign selectivity is established. Responses to AM and PM frequently summated nonlinearly, leading to sign-selective responses as a result of facilitation to the preferred sign of Df and/or suppression to the nonpreferred sign of Df. Facilitation typically occurred when responses to AM and PM were aligned, whereas suppression typically occurred when they were offset. By experimentally manipulating the degree of alignment between these two responses, we found that the summed response was dependent on their relative timing. In addition, we found a unique class of units that were sensitive to differences in amplitude between two body surfaces. This sensitivity rendered such units immune to the problem of orientation ambiguity, in which the sign selectivity of a single neuron reverses with changes in stimulus orientation. We discuss potential synaptic mechanisms for driving nonlinear responses in these and other combination-sensitive neurons.

This study examined the interactions between electrical stimuli presented through two channels of a cochlear implant. Experiments were conducted in anesthetized guinea pigs. Multiunit spike activity recorded from the auditory cortex reflected the cumulative effects of electric field interactions in the cochlea as well as any neural interactions along the ascending auditory pathway. The cochlea was stimulated electrically through a 6-electrode intracochlear array. The stimulus on each channel was a single 80- micro s/phase biphasic pulse. Channel interactions were quantified as changes in the thresholds for elevation of cortical spike rates. Experimental parameters were interchannel temporal offset (0 to +/-2000 micro s), interelectrode cochlear spacing (1.5 or 2.25 mm), electrode configuration (monopolar, bipolar, or tripolar), and relative polarity between channels (same or inverted). In most conditions, presentation of a subthreshold pulse on one channel reduced the threshold for a pulse on a second channel. Threshold shifts were greatest for simultaneous pulses, but appreciable threshold reductions could persist for temporal offsets up to 640 micro s. Channel interactions varied strongly with electrode configuration: threshold shifts increased in magnitude in the order tripolar, bipolar, monopolar. Channel interactions were greater for closer electrode spacing. The results have implications for design of speech processors for cochlear implants.

How do cortical neurons represent the acoustic environment? This question is often addressed by probing with simple stimuli such as clicks or tone pips. Such stimuli have the advantage of yielding easily interpreted answers, but have the disadvantage that they may fail to uncover complex or higher-order neuronal response properties. Here, we adopt an alternative approach, probing neuronal responses with complex acoustic stimuli, including animal vocalizations. We used in vivo whole-cell methods in the rat auditory cortex to record subthreshold membrane potential fluctuations elicited by these stimuli. Most neurons responded robustly and reliably to the complex stimuli in our ensemble. Using regularization techniques, we estimated the linear component, the spectrotemporal receptive field (STRF), of the transformation from the sound (as represented by its time-varying spectrogram) to the membrane potential of the neuron. We find that the STRF has a rich dynamical structure, including excitatory regions positioned in general accord with the prediction of the classical tuning curve. However, whereas the STRF successfully predicts the responses to some of the natural stimuli, it surprisingly fails completely to predict the responses to others; on average, only 11% of the response power could be predicted by the STRF. Therefore, most of the response of the neuron cannot be predicted by the linear component, although the response is deterministically related to the stimulus. Analysis of the systematic errors of the STRF model shows that this failure cannot be attributed to simple nonlinearities such as adaptation to mean intensity, rectification, or saturation. Rather, the highly nonlinear response properties of auditory cortical neurons must be attributable to nonlinear interactions between sound frequencies and time-varying properties of the neural encoder.

Mormyrid fish generate weak electric organ discharges (EODs) used for communication and navigation. EODs are initiated in the medullary command nucleus (CN), which receives dense projections from the mesencephalic precommand nucleus (PCN) and the adjacent thalamic dorsal posterior nucleus (DP), plus a minor projection from the ventral edge of the toral ventroposterior nucleus (VPv). The dorsal region of the ventroposterior nucleus (VPd) projects to DP-PCN and receives input from the electric organ corollary discharge pathway. I recorded extracellularly from single units within DP-PCN and VPd and correlated their activity patterns with electromotor output to generate hypotheses on electromotor control mechanisms. DP-PCN neurons show an oscillatory pattern of activity, firing within a window of 10-200 msec before each EOD, while remaining silent for 50-150 msec after each EOD. VPd neurons only fire during the silent period of DP-PCN neurons, suggesting that they provide recurrent inhibition to DP-PCN. During “scallops”, only DP-PCN neurons with high baseline firing rates increase their activity, whereas during “accelerations”, only neurons with low baseline firing rates show a strong increase in activity. Thus, the generation of different displays likely results from the activation of different groups of neurons projecting to CN. The activity of VPd neurons decreases during both displays, suggesting that disinhibition plays an important role in their generation. The mormyrid electromotor network shares many functional properties with central pattern generators (CPGs) found in relatively simple motor systems, indicating that it may be an excellent model system for studying CPG function in vertebrate communication.

The hedgehog tenrec, Echinops telfairi, has certain basal mammalian features, like a cloaca and a sparsely differentiated brain with smooth cerebral hemispheres. The peripheral auditory capabilities of this species were investigated by means of distortion product otoacoustic emissions (DPOAE). For comparison, we determined auditory evoked potentials (AEP) in the inferior colliculus and the auditory cortex. Both methods show that the auditory range of E. telfairi extends well into ultrasonic frequencies, with a region of highest sensitivity at around 16 kHz. The total auditory range spans about 4 octaves at 40 dB SPL. The low-frequency limit of auditory processing is found at frequencies of about 2-3 kHz. The DPOAE and the AEP thresholds of E. telfairi do not run fully parallel in the high-frequency range. For a threshold value of 40 dB SPL, cochlear mechanical thresholds as measured with DPOAE extend up to 50 kHz, whereas neuronal thresholds reach the high-frequency limit at about 30 kHz. Frequency tuning, as assessed from DPOAE suppression tuning curves, was low to moderate with Q(10 dB) values ranging from 1.7 to 8. The lack of discontinuity in the group delay (derived from DPOAE measurements) reveals that cochlear frequency representation is tonotopic without any region of specialized mechanical tuning.

The voltage-gated potassium (Kv) channel subunit Kv1.1, encoded by the Kcna1 gene, is expressed strongly in the ventral cochlear nucleus (VCN) and the medial nucleus of the trapezoid body (MNTB) of the auditory pathway. To examine the contribution of the Kv1.1 subunit to the processing of auditory information, in vivo single-unit recordings were made from VCN neurons (bushy cells), axonal endings of bushy cells at MNTB cells (calyces of Held), and MNTB neurons of Kcna1 -null (-/-) mice and littermate control (+/+) mice. Thresholds and spontaneous firing rates of VCN and MNTB neurons were not different between genotypes. At higher sound intensities, however, evoked firing rates of VCN and MNTB neurons were significantly lower in -/- mice than +/+ mice. The SD of the first-spike latency (jitter) was increased in VCN neurons, calyces, and MNTB neurons of -/- mice compared with +/+ controls. Comparison along the ascending pathway suggests that the increased jitter found in -/- MNTB responses arises mostly in the axons of VCN bushy cells and/or their calyceal terminals rather than in the MNTB neurons themselves. At high rates of sinusoidal amplitude modulations, -/- MNTB neurons maintained high vector strength values but discharged on significantly fewer cycles of the amplitude-modulated stimulus than +/+ MNTB neurons. These results indicate that in Kcna1 -null mice the absence of the Kv1.1 subunit results in a loss of temporal fidelity (increased jitter) and the failure to follow high-frequency amplitude-modulated sound stimulation in vivo .

We evaluated the spatial selectivity of auditory cortical neurons in awake cats. Single- and multiunit activity was recorded in primary auditory cortex as the animals performed a nonspatial auditory discrimination or sat idly. Their heads were unrestrained, and head position was tracked. Broadband sounds were delivered from locations throughout 360° on the horizontal plane, and source locations were expressed in head-centered coordinates. As in anesthetized animals, the firing rates of most units were modulated by sound location, and most units responded best to sounds in the contralateral hemifield. Tuning was sharper than in anesthetized cats, in part because of suppression at nonoptimal locations. Nonetheless, spatial receptive fields typically spanned 150-180°. Units exhibited diverse temporal response patterns that often depended on sound location. An information-theoretic analysis showed that information transmission was reduced by ∼10% when the precision of spike timing was disrupted by 16-32 msec, and by ∼50% when all location-related variation of spike timing was removed. Spikes occurring within 60 msec of stimulus onset transmitted the most location-related information, but later spikes also carried information. The amount of information transmitted by ensembles of units increased with the number of units, indicating some degree of mutual independence in the spatial information transmitted by various units. Spatial tuning and information transmission were changed little by an increase in sound level of 20-30 dB. For the vast majority of units, receptive fields showed no significant change with the cat's head position or level of participation in the auditory task.

The Zwicker tone (ZT) is defined as an auditory negative afterimage, perceived after the presentation of an appropriate inducer. Typically, a notched noise (NN) with a notch width of 1/2 octave induces a ZT with a pitch falling in the frequency range of the notch. The aim of the present study was to find potential neural correlates of the ZT in the primary auditory cortex of ketamine-anesthetized cats. Responses of multiunits were recorded simultaneously with two 8-electrode arrays during 1 s and over 2 s after the presentation of a white noise (WN) and three NNs differing by the width of the notch, namely, 1/3 octave (NN1), 1/2 octave (NN2), and 2/3 octave (NN3). Both firing rate (FR) and peak cross-correlation coefficient (p) were evaluated for time windows of 500 ms. The cortical units were grouped according to whether their characteristic frequency (CF) was inside ("In" neurons) or outside ("Out" neurons) a 1-octave-wide frequency band centered on the notch center frequency. The ratios between the FRs and the rhos for each NN and the WN condition and for each group of neurons were then statistically evaluated. The ratios of FRs were significantly increased during and after the presentation of the NN for the "In" neurons. In contrast, the changes for the t" neurons were small and most often insignificant. The ratios of the p values differed significantly from 1 in the "In-In" and "In-Out" groups during stimulation as well as after it. We also found that the ps of "Out" neurons were dependent on the type of NN. Potentially, a combination of increased p and increased FR might be a neurophysiological correlate of the ZT.

Neurons are often assumed to operate in a highly unreliable manner: a neuron can signal the same stimulus with a variable number of action potentials. However, much of the experimental evidence supporting this view was obtained in the visual cortex. We have, therefore, assessed trial-to-trial variability in the auditory cortex of the rat. To ensure single-unit isolation, we used cell-attached recording. Tone-evoked responses were usually transient, often consisting of, on average, only a single spike per stimulus. Surprisingly, the majority of responses were not just transient, but were also binary, consisting of 0 or 1 action potentials, but not more, in response to each stimulus; several dramatic examples consisted of exactly one spike on 100% of trials, with no trial-to-trial variability in spike count. The variability of such binary responses differs from comparably transient responses recorded in visual cortical areas such as area MT, and represent the lowest trial-to-trial variability mathematically possible for responses of a given firing rate. Our study thus establishes for the first time that transient responses in auditory cortex can be described as a binary process, rather than as a highly variable Poisson process. These results demonstrate that cortical architecture can support a more precise control of spike number than was previously recognized, and they suggest a re-evaluation of models of cortical processing that assume noisiness to be an inevitable feature of cortical codes.

The prevailing hierarchical model of cortical sensory processing holds that early processing is specific to individual modalities and that combination of information from different modalities is deferred until higher-order stages of processing. In this paper, we present physiological evidence of multisensory convergence at an early stage of cortical auditory processing. We used multi-neuron cluster recordings, along with a limited sample of single-unit recordings, to determine whether neurons in the macaque auditory cortex respond to cutaneous stimulation. We found coextensive cutaneous and auditory responses in caudomedial auditory cortex, an area lying adjacent to A1, and at the second stage of the auditory cortical hierarchy. Somatosensory-auditory convergence in auditory cortex may underlie effects observed in human studies. Convergence of inputs from different sensory modalities at very early stages of cortical sensory processing has important implications for both our developing understanding of multisensory processing and established views of unisensory processing.

A direct commissural connection between cochlear nuclei provides a pathway by which binaural input can influence the processing of acoustic information through the ventral cochlear nucleus. Despite anatomical evidence to suggest the existence of such a pathway, its nature and behavior have not been investigated previously. This in vivo intracellular electrophysiological study provides direct evidence of monosynaptic (mean latency, 1.43 msec), inhibitory commissural input to T stellate cells. This inhibition is fast acting (duration, <10 msec), occurring with little synaptic delay (∼0.3 msec). Electrical stimulation also revealed the initiation of antidromic responses in the onset chopper population, signifying D stellate neurons as a source of commissural inputs. Activation of the commissural connection was most evident in response to broadband stimuli. These results provide the first compelling evidence of a fast, monosynaptic commissural pathway arising from contralateral D stellate neurons providing broadband inhibitory input to T stellate cells.

The inferior colliculus (IC) is the first place in the central auditory pathway where duration-selective neurons are found. Previous neuropharmacological and electrophysiological studies have shown that they are created there and have led to a conceptual model in which excitatory and inhibitory inputs are offset in time so that the cell fires only when sound duration is such that onset- and offset-evoked excitation coincide; the response is suppressed by inhibition at other durations. We tested predictions from the model using paired tone stimulation and extracellular recording in the IC of the big brown bat, Eptesicus fuscus . Responses to a best duration (BD) tone were used as a probe to examine the strength and time course of inhibition activated by a nonexcitatory (NE) tone of the same frequency but differing in duration. As the relative time between the BD and NE tones was varied, the activity evoked by the BD tone was affected in ways comparable with backward, simultaneous, and forward masking. Responses to the BD tone were completely suppressed at short interstimulus intervals when the BD tone preceded the NE tone. Suppression was also seen when the stimuli temporally overlapped and summed and at intervals when the BD tone followed the NE tone. The results show that duration-selective neurons receive an onset-evoked, inhibitory input that precedes their excitatory input. The period of leading inhibition was correlated with BD and first spike latency. The results suggest how inhibition in the CNS could explain temporal masking phenomena, including backward masking.