Rat Primary Auditory Cortex Research Articles

Non-Gaussian Membrane Potential Dynamics Imply Sparse, Synchronous Activity in Auditory Cortex

Many models of cortical dynamics have focused on the high-firing regime, in which neurons are driven near their maximal rate. Here we consider the responses of neurons in auditory cortex under typical low-firing rate conditions, when stimuli have not been optimized to drive neurons maximally. We used whole-cell patch-clamp recording in vivo to measure subthreshold membrane potential fluctuations in rat primary auditory cortex in both the anesthetized and awake preparations. By analyzing the subthreshold membrane potential dynamics on single trials, we made inferences about the underlying population activity. We found that, during both spontaneous and evoked responses, membrane potential was highly non-Gaussian, with dynamics consisting of occasional large excursions (sometimes tens of millivolts), much larger than the small fluctuations predicted by most random walk models that predict a Gaussian distribution of membrane potential. Thus, presynaptic inputs under these conditions are organized into quiescent periods punctuated by brief highly synchronous volleys, or "bumps." These bumps were typically so brief that they could not be well characterized as "up states" or "down states." We estimate that hundreds, perhaps thousands, of presynaptic neurons participate in the largest volleys. These dynamics suggest a computational scheme in which spike timing is controlled by concerted firing among input neurons rather than by small fluctuations in a sea of background activity.

One Click, Two Clicks: The Past Shapes the Future in Auditory Cortex

What are the synaptic and cellular mechanisms by which stimulus context shapes cortical responses? In this issue of Neuron, Wehr and Zador describe intracellular recordings of responses to click pairs in rat primary auditory cortex (A1) and offer new insights into the successive roles of inhibition and synaptic depression in suppressing responses to the second click in many A1 neurons.

Affects of Aging on Receptive Fields in Rat Primary Auditory Cortex Layer V Neurons

Advanced age is commonly associated with progressive cochlear pathology and central auditory deficits, collectively known as presbycusis. The present study examined central correlates of presbycusis by measuring response properties of primary auditory cortex (AI) layer V neurons in the Fischer Brown Norway rat model. Layer V neurons represent the major output of AI to other cortical and subcortical regions (primarily the inferior colliculus). In vivo single-unit extracellular recordings were obtained from 114 neurons in aged animals (29-33 mo) and compared with 105 layer V neurons in young-adult rats (4-6 mo). Three consecutive repetitions of a pure-tone receptive field map were run for each neuron. Age was associated with fewer neurons exhibiting classic V/U-shaped receptive fields and a greater percentage of neurons with more Complex receptive fields. Receptive fields from neurons in aged rats were also less reliable on successive repetitions of the same stimulus set. Aging was also associated with less firing during the stimulus in V/U-shaped receptive field neurons and more firing during the stimulus in Complex neurons, which were generally associated with inhibited firing in young controls. Finally, neurons in aged rats with Complex receptive fields were more easily driven by current pulses delivered to the soma. Collectively, these findings provide support for the notion that age is associated with diminished signal-to-noise coding by AI layer V neurons and are consistent with other research suggesting that GABAergic neurotransmission in AI may be compromised by aging.

Age-related loss of the GABA synthetic enzyme glutamic acid decarboxylase in rat primary auditory cortex

Age-related changes within the auditory brainstem typically include alterations in inhibitory neurotransmission and coding mediated by GABA and glycinergic circuits. As part of an effort to evaluate the impact of aging on neurotransmission in the higher auditory centers, the present study examined age-related changes in the GABA synthetic enzyme, glutamic acid decarboxylase (GAD), in rat primary auditory cortex (AI), which contains a vast network of intrinsic and extrinsic GABAergic circuits throughout its layers. Message levels of the two GAD isoforms found in brain, GAD 65 and GAD 67, and GAD 67 protein levels were compared in young adult, middle-aged and aged rats using in situ hybridization and quantitative immunocytochemistry, respectively. For comparison, age-related GAD changes were also assessed in the parietal cortex and hippocampus. Significant age-related decreases in GAD 65&67 messages were observed in AI layers II–VI of aged rats relative to their young adult cohorts. The largest changes were identified in layer II (GAD 65: −26.6% and GAD 67: −40.1%). GAD 67 protein expression decreased significantly in parallel with mRNA decreases in all layers of AI. Adjacent regions of parietal cortex showed no significant GAD 67 protein changes among the age groups, except in layer IV. As previously described, GAD 67 message and protein levels in selected hippocampal regions were significantly reduced in aged rats. Age-related GAD reductions likely reflect decreases in both metabolic and pre-synaptic GABA levels suggesting a plastic down-regulation of normal adult inhibitory GABA neurotransmission. Consistent with the present findings, functional studies in primate visual cortex and preliminary studies in AI find coding changes suggestive of altered inhibitory processing in aged animals. An age-related loss of normal adult GABA neurotransmission in AI would likely alter temporal coding properties and could contribute to the loss in speech understanding observed in the elderly.

Divergent response properties of layer-V neurons in rat primary auditory cortex

Layer-V pyramidal cells comprise a major output of primary auditory cortex (A1). At least two cell types displaying different morphology, projections and in vitro physiology have been previously identified in layer-V. The focus of the present study was to characterize extracellular receptive field properties of layer-V neurons to determine whether a similar breakdown of responses can be found in vivo. Recordings from 105 layer-V neurons revealed two predominant receptive field types. Thirty-two percent displayed strong excitatory V/U-shaped receptive field maps and spiking patterns with shorter stimulus-driven interspike intervals (ISIs), reminiscent of the bursting cells discussed in the in vitro literature. V/U-shaped maps remained relatively unchanged across the three sequential repetitions of the map run on each neuron. Neurons with V/U-shaped maps were also easily depolarized with extracellular current pulse stimulation. In contrast, 47% of the neurons displayed Complex receptive field maps characterized by weak and/or inconsistent excitatory regions and were difficult to depolarize with current pulses. These findings suggest that V/U-shaped receptive fields could correspond to previously described intrinsic bursting (IB) cells with corticotectal projections, and that neurons with Complex receptive fields might represent the regular spiking (RS) cells with their greater inhibitory input and corticocortical/corticostriatal projection pattern.

Associative learning shapes the neural code for stimulus magnitude in primary auditory cortex

Since the dawn of experimental psychology, researchers have sought an understanding of the fundamental relationship between the amplitude of sensory stimuli and the magnitudes of their perceptual representations. Contemporary theories support the view that magnitude is encoded by a linear increase in firing rate established in the primary afferent pathways. In the present study, we have investigated sound intensity coding in the rat primary auditory cortex (AI) and describe its plasticity by following paired stimulus reinforcement and instrumental conditioning paradigms. In trained animals, population-response strengths in AI became more strongly nonlinear with increasing stimulus intensity. Individual AI responses became selective to more restricted ranges of sound intensities and, as a population, represented a broader range of preferred sound levels. These experiments demonstrate that the representation of stimulus magnitude can be powerfully reshaped by associative learning processes and suggest that the code for sound intensity within AI can be derived from intensity-tuned neurons that change, rather than simply increase, their firing rates in proportion to increases in sound intensity.

Complexity and temporal dynamics of frequency coding in the awake rat auditory cortex.

Auditory cortical neurons are elements of a neuronal network that decomposes sounds into spectral and temporal information. In particular, their frequency selectivity has been investigated in great detail. Most studies used anaesthetized preparations and found mainly simple V-shaped tuning. The few data available from awake animals indicate that more complex forms of spectral receptive fields, i.e. frequency response areas, can be found there. We investigated frequency response areas in the awake rat primary auditory cortex using statistical evaluation and found complex forms of frequency response areas with several separate subregions in many neurons, besides classical V-shaped tuning. Response areas, as determined with narrow band noise, were very similar to those measured with pure tones. Their width was well correlated to the response strength to white noise stimulation. These results suggest that the excitatory subregions of frequency response areas were the neurons' predominant characteristic, relevant also for the processing of more complex types of stimuli. Investigating the spectrotemporal dynamics of frequency response areas revealed that approximately one-third of the neurons showed long-lasting excitatory or inhibitory components in addition to the typical ON-response. Inhibition was usually of longer duration and occurred mainly in frequency ranges outside the range of initial excitatory responses. These results indicate that auditory cortical neurons in awake animals can represent spectrotemporal information of rather different complexity.

Intrinsic optical signals from rat primary auditory cortex in response to sound stimuli presented to contralateral, ipsilateral and bilateral ears.

In the auditory cortex, primitive features of acoustic stimuli are represented for auditory scene analysis. A typical example of a feature representation is the tonotopic map, in which sound frequencies are spatially arranged in an orderly manner. Some neurons in the auditory cortex are sensitive to sound source location, which is another important feature for auditory scene analysis. In the present study, using the intrinsic optical imaging technique, we attempted to visualize the two-dimensional pattern of neuronal population responses in the primary auditory cortex of rats to pure tones presented at various frequencies and sound intensities. The observed arrangements of sound frequencies were consistent with those obtained by electrophysiological mapping, which indicates that our intrinsic optical recording can visualize populational responses of neurons. We also found different temporal patterns of intrinsic signals elicited in response to contralateral, ipsilateral, and bilateral ear stimulations. Finally we try to explain the observed differential time courses of intrinsic signal responses from the theoretical point of view on the conduction of neural activities, based on the so far anatomically identified neural pathways in the rodent auditory system.

Persistent and specific influences of early acoustic environments on primary auditory cortex.

This study demonstrates that the adult form of 'tonotopic maps' of sound frequency in the rat primary auditory cortex (A1) arises from parallel developmental processes involving two cortical zones: the progressive differentiation and refinement of selectively tone-responsive receptive fields within an initially broadly-tuned posterior zone, and the progressive loss of tone-evoked, short-latency response over an initially large, very broadly tuned anterior zone. The formation of tonotopic maps in A1 was specifically influenced by a rat pup's early acoustic environments. Exposure to pulsed tones resulted in accelerated emergence and an expansion of A1 representations of those specific tone frequencies, as well as a deteriorated tonotopicity and broader-than-normal receptive fields. Thus, auditory experiences during early postnatal development are important in shaping the functional development of auditory cortical representations of specific acoustic environments.

Analysis of Transient Expression of Estrogen Receptor-α in Newborn Rat Primary Auditory Cortex

In the primary temporal cortex (Te1) of newborn rats, we detected transient expression of α-type estrogen receptor (ERα). Since they have a pyramidal-like shape, they are considered neurons. By immunohistochemistry we found that they were absolutely devoid of glial fibrillary acidic protein but some of them contained calretinin, a calcium binding protein. It is already known that neurons in layer V of the Te1 extend their projections to the contralateral side of the Te1, the ipsilateral inferior colliculus, or the ipsilateral medial geniculate nucleus. Thus, we applied a retrograde track tracer into those regions of newborn rats and examined the possible colocalization of ERα signals and the tracer in the same cells. So far no clear colocalization of both signals has been detected in cells in the Te1. Thus, the cells expressing ERα transiently are not projecting to the assumed regions, at least at the newborn age examined in the present experiment. The possibility exists that (1) they are not projection neurons but local interneurons, (2) even though they are projection neurons, they did not have any synaptic contacts with their target region(s), (3) they may die after they are attached to the target neurons. Further analyses are needed to clarify the biological roles of ERα expressed transiently in these neurons. On the other hand, no ERβ cells were detected in the same region of the brain under the same condition. Thus, this finding was limited to the ERα.

Anesthesia changes frequency tuning of neurons in the rat primary auditory cortex.

The vast majority of investigations on central auditory processing so far were conducted under the influence of an anesthetic agent. It remains unclear, however, to what extend even basic response properties of central auditory neurons are influenced by this experimental manipulation. We used a combination of chronic recording in unrestrained animals, computer-controlled randomized acoustic stimulation, and statistical evaluation of responses to directly compare the response characteristics of single neurons in the awake and anesthetized state. Thereby we were able to quantify the effects of pentobarbital/chloral hydrate anesthesia (Equithesin) on rat auditory cortical neurons. During Equithesin anesthesia, only a portion of central neurons were active and some of their basic response properties were changed. Only 29% of the neurons still had a frequency response area. Their tuning sharpness was increased under anesthesia. Most changes are consistent with an enhancement of inhibitory influences during Equithesin anesthesia. Thus when describing response properties of central auditory neurons, the animal's anesthetic state has to be taken into account.

Role of mammalian auditory cortex in the perception of elementary sound properties.

Studies in several mammalian species have demonstrated that bilateral ablations of the auditory cortex have little effect on simple sound intensity and frequency-based behaviors. In the rat, for example, early experiments have shown that auditory ablations result in virtually no effect on the rat's ability to either detect tones or discriminate frequencies. Such lesion experiments, however, typically examine an animal's performance some time after recovery from ablation surgery. As such, they demonstrate that the cortex is not essential for simple auditory behaviors in the long run. Our study further explores the role of cortex in basic auditory perception by examining whether the cortex is normally involved in these behaviors. In these experiments we reversibly inactivated the rat primary auditory cortex (AI) using the GABA agonist muscimol, while the animals performed a simple auditory task. At the same time we monitored the rat's auditory activity by recording auditory evoked potentials (AEP) from the cortical surface. In contrast to lesion studies, the rapid time course of these experimental conditions preclude reorganization of the auditory system that might otherwise compensate for the loss of cortical processing. Soon after bilateral muscimol application to their AI region, our rats exhibited an acute and profound inability to detect tones. After a few hours this state was followed by a gradual recovery of normal hearing, first of tone detection and, much later, of the ability to discriminate frequencies. Surface muscimol application, at the same time, drastically altered the normal rat AEP. Some of the normal AEP components vanished nearly instantaneously to unveil an underlying waveform, whose size was related to the severity of accompanying behavioral deficits. These results strongly suggest that the cortex is directly involved in basic acoustic processing. Along with observations from accompanying multiunit experiments that related the AEP to AI neuronal activity, our results suggest that a critical amount of activity in the auditory cortex is necessary for normal hearing. It is likely that the involvement of the cortex in simple auditory perceptions has hitherto not been clearly understood because of underlying recovery processes that, in the long-term, safeguard fundamental auditory abilities after cortical injury.

Distributed representation of spectral and temporal information in rat primary auditory cortex

Modulations of amplitude and frequency are common features of natural sounds, and are prominent in behaviorally important communication sounds. The mammalian auditory cortex is known to contain representations of these important stimulus parameters. This study describes the distributed representations of tone frequency and modulation rate in the rat primary auditory cortex (A1). Detailed maps of auditory cortex responses to single tones and tone trains were constructed from recordings from 50–60 microelectrode penetrations introduced into each hemisphere. Recorded data demonstrated that the cortex uses a distributed coding strategy to represent both spectral and temporal information in the rat, as in other species. Just as spectral information is encoded in the firing patterns of neurons tuned to different frequencies, temporal information appears to be encoded using a set of filters covering a range of behaviorally important repetition rates. Although the average A1 repetition rate transfer function (RRTF) was low-pass with a sharp drop-off in evoked spikes per tone above 9 pulses per second (pps), individual RRTFs exhibited significant structure between 4 and 10 pps, including substantial facilitation or depression to tones presented at specific rates. No organized topography of these temporal filters could be determined.

Sensitivity to simulated directional sound motion in the rat primary auditory cortex.

Sensitivity to simulated directional sound motion in the rat primary auditory cortex. This paper examines neuron responses in rat primary auditory cortex (AI) during sound stimulation of the two ears designed to simulate sound motion in the horizontal plane. The simulated sound motion was synthesized from mathematical equations that generated dynamic changes in interaural phase, intensity, and Doppler shifts at the two ears. The simulated sounds were based on moving sources in the right frontal horizontal quadrant. Stimuli consisted of three circumferential segments between 0 and 30 degrees, 30 and 60 degrees, and 60 and 90 degrees and four radial segments at 0, 30, 60, and 90 degrees. The constant velocity portion of each segment was 0.84 m long. The circumferential segments and center of the radial segments were calculated to simulate a distance of 2 m from the head. Each segment had two trajectories that simulated motion in both directions, and each trajectory was presented at two velocities. Young adult rats were anesthetized, the left primary auditory cortex was exposed, and microelectrode recordings were obtained from sound responsive cells in AI. All testing took place at a tonal frequency that most closely approximated the best frequency of the unit at a level 20 dB above the tuning curve threshold. The results were presented on polar plots that emphasized the two directions of simulated motion for each segment rather than the location of sound in space. The trajectory exhibiting a "maximum motion response" could be identified from these plots. "Neuron discharge profiles" within these trajectories were used to demonstrate neuron activity for the two motion directions. Cells were identified that clearly responded to simulated uni- or multidirectional sound motion (39%), that were sensitive to sound location only (19%), or that were sound driven but insensitive to our location or sound motion stimuli (42%). The results demonstrated the capacity of neurons in rat auditory cortex to selectively process dynamic stimulus conditions representing simulated motion on the horizontal plane. Our data further show that some cells were responsive to location along the horizontal plane but not sensitive to motion. Cells sensitive to motion, however, also responded best to the moving sound at a particular location within the trajectory. It would seem that the mechanisms underlying sensitivity to sound location as well as direction of motion converge on the same cell.

Origins of medial geniculate body projections to physiologically defined zones of rat primary auditory cortex

Medial geniculate body neurons projecting to physiologically identified subregions of rat primary auditory cortex (area 41, Te1) were labeled with horseradish peroxidase in adult rats. The goals were to determine the type(s) of projection neuron and the spatial arrangement of these cells with respect to thalamic subdivisions. Maps of best frequency were made with single neuron or unit cluster extracellular recording at depths of 500–800 μm, which correspond to layers III–IV in Nissl preparations. Tracer injections were made in different cortical isofrequency regions (2, 11, 22, or 38 kHz, respectively). Labeled neurons were plotted on representative sections upon which the architectonic subdivisions were drawn independently. Most of the cells of origin lay in the ventral division in every experiment. Injections at low frequencies labeled bands of neurons laterally in the ventral division; progressively more rostral deposits at higher frequencies labeled bands or clusters more medially in the ventral division, and through most of its caudo-rostral extent. Medial division labeling was variable. Labeled cells were always in the lateral half of the nucleus and were often scattered. There were few labeled cells in the dorsal division. Seven types of thalamocortical neuron were identified: ventral division cells had a tufted branching pattern, while medial division neurons have heterogeneous shapes and sizes and were larger. Dorsal division neurons had a radiate branching pattern. The size range of labeled neurons spanned that of Nissl stained neuronal somata. Area 41 may receive two types of thalamic projection: ventral division input is strongly convergent, highly topographic, spatially focal, and restricted to one type of neuron only, while the medial division projection is more divergent, coarsely topographical, involves multiple cortical areas, and has several varieties of projection neuron. Despite species differences in local circuitry, many facets of thalamocortical organization are conserved in phylogeny.

Plasticity of temporal information processing in the primary auditory cortex.

Neurons in the rat primary auditory cortex (A1) generally cannot respond to tone sequences faster than 12 pulses per second (pps). To test whether experience can modify this maximum following rate in adult rats, trains of brief tones with random carrier frequency but fixed repetition rate were paired with electrical stimulation of the nucleus basalis (NB) 300 to 400 times per day for 20-25 days. Pairing NB stimulation with 5-pps stimuli markedly decreased the cortical response to rapidly presented stimuli, whereas pairing with 15-pps stimuli significantly increased the maximum cortical following rate. In contrast, pairing with fixed carrier frequency 15-pps trains did not significantly increase the mean maximum following rate. Thus this protocol elicits extensive cortical remodeling of temporal response properties and demonstrates that simple differences in spectral and temporal features of the sensory input can drive very different cortical reorganizations.

Responses to time-varying stimuli in rat auditory cortex

Responses to frequency modulated (FM) sweeps were recorded in rat primary auditory cortex. Forty-four percent of the cells were direction-selective. For speed selectivity, the majority of the cells preferred faster sweeps. The results suggest that rat auditory cortex may be used for processing communication signals of their predators or for detecting spectral changes in acoustic signals.

Pyramidal cells in rat temporoauditory cortex project to both striatum and inferior colliculus

A retrograde fluorescent double-labeling technique was employed to examine whether the corticostriate fibers are collaterals of the corticofugal fibers directed to the inferior colliculus in the rat. Following injections of two different fluorescent tracers into the striatum and the inferior colliculus, double-labeled cells were found in layer V pyramidal cells of the temporal cortex. These double-labeled cells were located mostly in the area corresponding to the rat primary auditory cortex, and constituted 6.4% of the pyramidal cells projecting to the inferior colliculus. This study has revealed the existence of a common innervation of the basal ganglia and the auditory system by the pyramidal cell of the auditory cortex.