Callosal connections of the ferret primary auditory cortex

 The callosal connections of ferret auditory cortex were studied by making multiple injections of wheat germ agglutinin-horseradish peroxidase into the middle ectosylvian gyrus or by packing crystals of horseradish peroxidase into the transected corpus callosum. The primary area (AI) had strong callosal connections that arose from somata mainly located in layer III. Other layers contained sparsely distributed cells that projected across the midline. The projecting cells occurred over the whole extent of AI but were not homogeneously distributed in layer III. The axons from these cells terminated mainly in the upper layers of the contralateral cortex, where they converged onto three discrete bands. The three elongated bands lay in a dorsoventral orientation, parallel to the tonotopic axis. They were slightly curved and had a fairly uniform width. The posterior band had a width of about 200 μm, while the anterior and middle bands were more variable and had widths of 300–800 μm. The centre-to-centre distance between the posterior and middle bands was 520 ± 60 μm and for the anterior to middle bands was 620 ± 210 μm. The retrograde labelling produced by the same injections showed that the cell bodies had a higher density in the terminal bands than in the intervening spaces. The bands of dense callosal connections appear to correspond to the binaural summation columns, which have been clearly demonstrated in the ferret, but direct evidence of this will need to be sought in a future study. The discrete nature of the callosal bands in the ferret appears to make it a suitable species for studying the relationship between callosal terminals and those arising in other areas of the brain and for clarifying the possible existence of separate functional systems within the auditory cortex. Received: 23 September 1996 / Accepted: 17 March 1997     

Nonlinearity of coding in primary auditory cortex of the awake ferret

Neural computation in sensory systems is often modeled as a linear system. This first order approximation is computed by reverse correlating a stimulus with the spike train it evokes. The spectro-temporal receptive field (STRF) is a generalization of this procedure which characterizes processing in the auditory pathway in both frequency and time. While the STRF performs well in predicting the overall course of the response to a novel stimulus, it is unable to account for aspects of the neural output which are inherently nonlinear (e.g. discrete events and non-negative spike rates). We measured the STRFs of neurons in the primary auditory cortex (AI) of the awake ferret using spectro-temporally modulated auditory gratings, or ripples. We quantified the degree of nonlinearity of these neurons by comparing their responses to the responses predicted from their respective STRFs. The responses of most cells in AI exhibited a squaring, nonlinear relation to the stimuli used to evoke them. Thus, the nonlinearity of these cells was nontrivial, that is it was not solely the result of spike rate rectification or saturation. By modeling the nonlinearity as a polynomial static output function, the predictive power of the STRF was significantly improved.     

Deoxyglucose uptake in the ferret auditory cortex

Histological methods and 2-deoxyglucose autoradiography were used in an attempt at finding distinguishing characteristics that would permit the clear definition of different auditory areas on the ectosylvian gyrus. This region was studied in both coronal and flattened tangential sections. In tangential sections a crescent-shaped region of high deoxyglucose uptake was identified. The centre of this crescent was in the position of the primary auditory area on the middle ectosylvian gyrus. The ventro-anterior arm of the crescent was on the surface of the anterior ectosylvian gyrus and the ventro-posterior arm on the posterior ectosylvian gyrus. All three parts of the crescent appear to have an auditory function, because ablating the inferior colliculus or inserting a contralateral earplug reduced their deoxyglucose uptake. This was shown by using two separately distinguishable forms of 2-deoxyglucose, incorporating the ¹⁸F and ¹⁴C isotopes. In addition, another area of high deoxyglucose activity was identified in the ventral wall of the suprasylvian sulcus, which seems to correspond to the anterior auditory field. These four areas with high deoxyglucose uptake also have high levels of succinate dehydrogenase activity and moderately high densities of myelinated fibres. Succinate dehydrogenase histochemistry provides a simple method for identifying auditory cortical areas and should be of use in future physiological studies. These results provide evidence that the ferret has four separate auditory areas with relatively high metabolic and functional activity. Received: 8 August 1996 / Accepted: 15 May 1997     

Spectro-temporal response field characterization with dynamic ripples in ferret primary auditory cortex

To understand the neural representation of broadband, dynamic sounds in primary auditory cortex (AI), we characterize responses using the spectro-temporal response field (STRF). The STRF describes, predicts, and fully characterizes the linear dynamics of neurons in response to sounds with rich spectro-temporal envelopes. It is computed from the responses to elementary "ripples," a family of sounds with drifting sinusoidal spectral envelopes. The collection of responses to all elementary ripples is the spectro-temporal transfer function. The complex spectro-temporal envelope of any broadband, dynamic sound can expressed as the linear sum of individual ripples. Previous experiments using ripples with downward drifting spectra suggested that the transfer function is separable, i.e., it is reducible into a product of purely temporal and purely spectral functions. Here we measure the responses to upward and downward drifting ripples, assuming reparability within each direction, to determine if the total bidirectional transfer function is fully separable. In general, the combined transfer function for two directions is not symmetric, and hence units in AI are not, in general, fully separable. Consequently, many AI units have complex response properties such as sensitivity to direction of motion, though most inseparable units are not strongly directionally selective. We show that for most neurons, the lack of full separability stems from differences between the upward and downward spectral cross-sections but not from the temporal cross-sections; this places strong constraints on the neural inputs of these AI units.     

Encoding of virtual acoustic space stimuli by neurons in ferret primary auditory cortex

Recent studies from our laboratory have indicated that the spatial response fields (SRFs) of neurons in the ferret primary auditory cortex (A1) with best frequencies > or =4 kHz may arise from a largely linear processing of binaural level and spectral localization cues. Here we extend this analysis to investigate how well the linear model can predict the SRFs of neurons with different binaural response properties and the manner in which SRFs change with increases in sound level. We also consider whether temporal features of the response (e.g., response latency) vary with sound direction and whether such variations can be explained by linear processing. In keeping with previous studies, we show that A1 SRFs, which we measured with individualized virtual acoustic space stimuli, expand and shift in direction with increasing sound level. We found that these changes are, in most cases, in good agreement with predictions from a linear threshold model. However, changes in spatial tuning with increasing sound level were generally less well predicted for neurons whose binaural frequency-time receptive field (FTRF) exhibited strong excitatory inputs from both ears than for those in which the binaural FTRF revealed either a predominantly inhibitory effect or no clear contribution from the ipsilateral ear. Finally, we found (in agreement with other authors) that many A1 neurons exhibit systematic response latency shifts as a function of sound-source direction, although these temporal details could usually not be predicted from the neuron's binaural FTRF.     

Listening through different ears alters spatial response fields in ferret primary auditory cortex

The localization of sounds in space is based on spatial cues that arise from the acoustical properties of the head and external ears. Individual differences in localization cue values result from variability in the shape and dimensions of these structures. We have mapped spatial response fields of high-frequency neurons in ferret primary auditory cortex using virtual sound sources based either on the animal's own ears or on the ears of other subjects. For 73% of units, the response fields measured using the animals' own ears differed significantly in shape and/or position from those obtained using spatial cues from another ferret. The observed changes correlated with individual differences in the acoustics. These data are consistent with previous reports showing that humans localize less accurately when listening to virtual sounds from other individuals. Together these findings support the notion that neural mechanisms underlying auditory space perception are calibrated by experience to the properties of the individual.     

Stability of spectro-temporal tuning over several seconds in primary auditory cortex of the awake ferret

The steady-state spectro-temporal tuning of auditory cortical cells has been studied using a variety of broadband stimuli that characterize neurons by their steady-state responses to long duration stimuli, lasting from about a second to several minutes. Central sensory stations are thought to adapt in their response to stimuli presented over extended periods of time. For instance, we have previously shown that auditory cortical neurons display a second order of adaptation, whereby the rate of their adaptation to the repeated presentation of fixed alternating stimuli decreases with each presentation. The auditory grating (or ripple) method of characterizing central auditory neurons, and its extensions, have proven very effective. But these stimuli are typically used with spectro-temporal content held fixed over time-scales of seconds, introducing the possibility of rapid adaptation while the receptive field is being measured, whereas the neural response used to compute a spectro-temporal receptive field (STRF) assumes stationarity in the neural input/output function. We demonstrate dynamic changes in some parameters during the measurement of the STRF over a period of seconds, even absent of a relevant behavioral task. Specifically, we find in the primary auditory cortex of the awake ferret, small but systematic changes in duration and breadth of tuning of STRFs when comparing the early (0.25-1.75 s) and late (4.5-6 s) segments of the responses to these stimuli.     

Modulation of thalamic auditory neurons by the primary auditory cortex

The central auditory system consists of the lemniscal and nonlemniscal pathways or systems, which are anatomically and physiologically different from each other. In the thalamus, the ventral division of the medial geniculate body (MGBv) belongs to the lemniscal system, whereas its medial (MGBm) and dorsal (MGBd) divisions belong to the nonlemniscal system. Lemniscal neurons are sharply frequency-tuned and provide highly frequency-specific information to the primary auditory cortex (AI), whereas nonlemniscal neurons are generally broadly frequency-tuned and project widely to cortical auditory areas including AI. These two systems are presumably different not only in auditory signal processing, but also in eliciting cortical plastic changes. Electric stimulation of narrowly frequency-tuned MGBv neurons evokes the shift of the frequency-tuning curves of AI neurons toward the tuning curves of the stimulated MGBv neurons (tone-specific plasticity). In contrast, electric stimulation of broadly frequency-tuned MGBm neurons augments the auditory responses of AI neurons and broadens their frequency-tuning curves (nonspecific plasticity). In our current studies, we found that electric stimulation of AI evoked tone-specific plastic changes of the MGBv neurons, whereas it degraded the frequency tuning of MGBm neurons by inhibiting their auditory responses. AI apparently modulates the lemniscal and nonlemniscal thalamic neurons in quite different ways. High MGBm activity presumably makes AI neurons less favorable for fine auditory signal processing, whereas high MGBv activity makes AI neurons more suitable for fine processing of specific auditory signals and reduces MGBm activity.     

Chemoarchitectonic organization of the cat primary auditory cortex

Summary Acetylcholinesterase (AChE) activity, demonstrated histochemically, defines an area of cortex on the middle ectosylvian gyrus that appears to correspond to the cytoarchitectonically defined area 41 and the physiologically defined primary auditory area (AI). In this area there are high levels of AChE in layers III, IV and VI while in the surrounding areas there are comparatively low levels of enzyme in these layers. The monoclonal antibody CAT 301, which was raised against a cell surface proteoglycan, also defines this area. There are high levels of CAT 301 immunoreactivity in cell bodies and the neuropil of layer III and an absence of very large immunoreactive neurons in layer V. Furthermore there are higher levels of the calcium binding protein, parvalbumin and the metabolic enzyme, cytochrome oxidase, in layers III and IV of AI, than in most of the surrounding cortex. By contrast the distribution of the calcium binding protein, calbindin and the distribution of myelinated fibers are similar in area 41 and the surrounding areas.     

Binaural interaction revisited in the cat primary auditory cortex

The binaural interactions of neurons were studied in the primary auditory cortex (AI) of barbiturate-anesthetized cats with a matrix of binaural tonal stimuli varying in both interaural level differences (ILD) and average binaural level (ABL). The purpose of this study was to determine: 1) the distribution of preferred binaural combinations (PBCs) of a large population of neurons and its relationships with binaural interactions and binaural monotonicity; 2) whether monaural responses are predictive of binaural responses; and 3) whether there is a restricted set of representative binaural stimulus configurations that could effectively classify the binaural interactions. Binaural interactions were often diverse in the matrix and dependent on both ABL and ILD. Compared with previous studies, a higher proportion of mixed binaural interaction type and a lower proportion of EO/I type were found. No monaural neurons were found. Binaural responses often differed from monaural responses in the number of spikes and/or the form of the response functions. The PBCs of the majority of EO and PB neurons were in the contralateral field and midline, respectively. However, the PBCs of EE units were evenly distributed across the contralateral and ipsilateral fields. The majority of the nonmonotonic neurons responded most strongly to lower ABLs, whereas the majority of monotonic neurons responded most strongly to higher ABLs. This study demonstrated that in AI a restricted set of binaural stimulus configurations is not sufficient to reveal the binaural responses properties. Also, monaural responses are not predictive of binaural responses.     

Coding of amplitude modulation in primary auditory cortex

Conflicting results have led to different views about how temporal modulation is encoded in primary auditory cortex (A1). Some studies find a substantial population of neurons that change firing rate without synchronizing to temporal modulation, whereas other studies fail to see these nonsynchronized neurons. As a result, the role and scope of synchronized temporal and nonsynchronized rate codes in AM processing in A1 remains unresolved. We recorded A1 neurons' responses in awake macaques to sinusoidal AM noise. We find most (37-78%) neurons synchronize to at least one modulation frequency (MF) without exhibiting nonsynchronized responses. However, we find both exclusively nonsynchronized neurons (7-29%) and "mixed-mode" neurons (13-40%) that synchronize to at least one MF and fire nonsynchronously to at least one other. We introduce new measures for modulation encoding and temporal synchrony that can improve the analysis of how neurons encode temporal modulation. These include comparing AM responses to the responses to unmodulated sounds, and a vector strength measure that is suitable for single-trial analysis. Our data support a transformation from a temporally based population code of AM to a rate-based code as information ascends the auditory pathway. The number of mixed-mode neurons found in A1 indicates this transformation is not yet complete, and A1 neurons may carry multiplexed temporal and rate codes.     

Contribution of auditory cortex to sound localization by the ferret (Mustela putorius)

Ferrets were tested in a semicircular apparatus to determine the effects of auditory cortical lesions on their ability to localize sounds in space. They were trained to initiate trials while facing forward in the apparatus, and sounds were presented from one of two loudspeakers located in the horizontal plane. Minimum audible angles were obtained for three different positions, viz., the left hemifield, with loudspeakers centered around -60 degrees azimuth; the right hemifield, with loudspeakers centered around +60 degrees azimuth; and the midline with loudspeakers centered around 0 degrees azimuth. Animals with large bilateral lesions had severe impairments in localizing a single click in the midline test. Following complete destruction of the auditory cortex performance was only marginally above the level expected by chance even at large angles of speaker separation. Severe impairments were also found in localization of single clicks in both left and right lateral fields. In contrast, bilateral lesions restricted to the primary auditory cortex resulted in minimal impairments in midline localization. The same lesions, however, produced severe impairments in localization of single clicks in both left and right lateral fields. Large unilateral lesions that destroyed auditory cortex in one hemisphere resulted in an inability to localize single clicks in the contralateral hemifield. In contrast, no impairments were found in the midline test or in the ipsilateral hemifield. Unilateral lesions of the primary auditory cortex resulted in severe contralateral field deficits equivalent to those seen following complete unilateral destruction of auditory cortex. No deficits were seen in either the midline or the ipsilateral tests.     

Modality-independent role of the primary auditory cortex in time estimation

It has been argued that both modality-specific and supramodal mechanisms dedicated to time perception underlie the estimation of interval durations. While it is generally assumed that early sensory areas are dedicated to modality-specific time estimation, we hypothesized that early sensory areas such as the primary visual cortex or the auditory cortex might be involved in time perception independently of the sensory modality of the input. To test this possibility, we examined whether disruption of the primary visual cortex or the auditory cortex would disrupt time estimation of auditory stimuli and visual stimuli using transcranial magnetic stimulation (TMS). We found that disruption of the auditory cortex impaired not only time estimation of auditory stimuli but also impaired that of visual stimuli to the same degree. This finding suggests a supramodal role of the auditory cortex in time perception. On the other hand, TMS over the primary visual cortex impaired performance only in visual time discrimination. These asymmetric contributions of the auditory and visual cortices in time perception may be explained by a superiority of the auditory cortex in temporal processing. Here, we propose that time is primarily encoded in the auditory system and that visual inputs are automatically encoded into an auditory representation in time discrimination tasks.     

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.