Physiological and behavioral studies of spatial coding in the auditory cortex

Abstract

Despite extensive subcortical processing, the auditory cortex is believed to be essential for normal sound localization. However, we still have a poor understanding of how auditory spatial information is encoded in the cortex and of the relative contribution of different cortical areas to spatial hearing. We investigated the behavioral consequences of inactivating ferret primary auditory cortex (A1) on auditory localization by implanting a sustained release polymer containing the GABA(A) agonist muscimol bilaterally over A1. Silencing A1 led to a reversible deficit in the localization of brief noise bursts in both the horizontal and vertical planes. In other ferrets, large bilateral lesions of the auditory cortex, which extended beyond A1, produced more severe and persistent localization deficits. To investigate the processing of spatial information by high-frequency A1 neurons, we measured their binaural-level functions and used individualized virtual acoustic space stimuli to record their spatial receptive fields (SRFs) in anesthetized ferrets. We observed the existence of a continuum of response properties, with most neurons preferring contralateral sound locations. In many cases, the SRFs could be explained by a simple linear interaction between the acoustical properties of the head and external ears and the binaural frequency tuning of the neurons. Azimuth response profiles recorded in awake ferrets were very similar and further analysis suggested that the slopes of these functions and location-dependent variations in spike timing are the main information-bearing parameters. Studies of sensory plasticity can also provide valuable insights into the role of different brain areas and the way in which information is represented within them. For example, stimulus-specific training allows accurate auditory localization by adult ferrets to be relearned after manipulating binaural cues by occluding one ear. Reversible inactivation of A1 resulted in slower and less complete adaptation than in normal controls, whereas selective lesions of the descending cortico collicular pathway prevented any improvement in performance. These results reveal a role for auditory cortex in training-induced plasticity of auditory localization, which could be mediated by descending cortical pathways.

Fig. 1

(a) Lateral view of the ferret brain showing the major sulci and gyri. (b) Sensory cortical areas in the ferret. The locations of known auditory, visual, somatosensory and posterior parietal fields are indicated. Scale bar = 5 mm in a and 1mm in b, respectively. (Abbreviations: AEG, anterior ectosylvian gyrus; ASG, anterior sigmoid gyrus; as, ansinate sulcus; cns, coronal sulcus; crs, cruciate sulcus; LG, lateral gyrus; ls, lateral sulcus; MEG, middle ectosylvian gyrus; OB, olfactory bulb; OBG, orbital gyrus; PEG, posterior ectosylvian gyrus; prs, presylvian sulcus; PSG, posterior sigmoid gyrus; pss, pseudosylvian sulcus; SSG, suprasylvian gyrus, sss, suprasylvian sulcus; A1, primary auditory cortex; AAF, anterior auditory field; PPF, posterior pseudosylvian field; PSF, posterior suprasylvian field; ADF, anterior dorsal field; AVF, anterior ventral field; SSY, suprasylvian field; fAES, anterior ectosylvian sulcal field; PPc, caudal posterior parietal cortex; PPr, rostral posterior parietal cortex; 3b, primary somatosensory cortex; S2, secondary somatosensory cortex; S3, tertiary somatosensory cortex; D, dorsal; R, rostral.)

Fig. 2

The auditory cortex is needed for normal sound localization: (a) Setup used for measuring localization in the horizontal plane. Ferrets were trained to stand on the start platform and initiate a trial by licking the start spout. Each trial consisted of a broadband noise burst of variable duration and level presented randomly from 1 of 12 speakers positioned at 30° intervals in the horizontal plane. The animals were rewarded for approaching and licking the reward spout associated with the speaker that had been triggered. (b) The polar plot shows the mean percentage scores achieved when localizing 40-ms noise bursts by a group of four control ferrets and four animals in which A1 had been inactivated bilaterally by placing sheets of a slow-release polymer containing the GABA_A agonist muscimol on the cortex. These animals achieved lower scores than the normal controls at all stimulus angles. From Smith et al. (2004). (c) Setup used for measuring localization in the vertical plane. The animals had to discriminate between stimuli presented from one of two speakers positioned in the midsagittal plane. Because it was not possible for the animals to approach the sound-source directly, they were rewarded for responding at a reward spout to their right (90°) when the sound was presented from the upper speaker, and at a spout to their left (270°) when sound was presented from the lower speaker. (d) Psychometric functions fitted to the data from the same ferrets before (control) and after inactivating A1 bilaterally with muscimol-Elvax. In five (out of six) animals contributing to these data, A1 inactivation produced a significant drop in performance. From Bizley et al. (submitted).

Fig. 3

Examples of neuronal sensitivity to interaural level differences (ILDs) in A1 of anesthetized ferrets: (a, b) Neurons sensitive to ILDs favoring the contralateral ear. (c, d) Neurons sensitive predominantly to average binaural level (ABL), but less so to ILD. (e, f) Neurons with non-monotonic responses in both ILD and ABL. The gray scale indicates the mean evoked spike rate (Hz) per stimulus presentation. Negative rates are sound level combinations for which the evoked spike rate was below spontaneous levels. To aid visualization, response surfaces were smoothed with a low-pass filter (2D Gaussian, σ = 0.66) and interpolated. These examples are not members of discrete classes since principal components analysis of the population of binaural response function shapes reveals a continuous distribution of response properties (g, h). From Campbell et al. (2006).

Fig. 4

Predicting spatial responses from the frequency tuning of neurons in A1. Examples of frequency-time response fields (FTRFs) for each ear (a), together with the observed (b) and predicted (c) spatial receptive fields (SRFs) of a neuron recorded in A1 of an anesthetized ferret. The FTRFs were measured by reverse correlation to random chord stimuli presented to each ear. The observed SRFs were generated by presenting noise bursts from 224 virtual sound directions, covering 360° in azimuth and from –60° to +90° in elevation. The predicted SRFs were generated by convolving the FTRFs with the energy spectrum vectors of the VAS stimuli for each ear and each position in space (from Schnupp et al., 2001).

Fig. 5

Spatial selectivity in A1 of awake ferrets: (a) Raster plot showing the response of one unit to free-field stimuli presented at the azimuthal angles given on the ordinate. Positive numbers indicate the right hemifield and negative numbers locations to the animal’s left. Each dot represents the time of occurrence of an action potential, as shown on the abscissa. Each row of dots indicates the spike pattern for a single presentation of a 100-ms noise burst, which began at 0 ms. (b) Azimuth response profile for this unit, which was smoothed by fitting with a von Mises (von Mis in key) spherical function. This unit was recorded in the left A1 and was broadly tuned to the contralateral hemifield. Centroid direction vectors indicate the overall directional preference of the response profiles and were calculated by modeling the response profile as a circle of unit radius, whose “mass density” in each direction was given by the observed response strength in the corresponding direction. These are shown in c and d for all units recorded from three diVerent animals and plotted according to the sound level used and the hemisphere in which they were recorded.

Fig. 6

Plasticity of spatial hearing in adult ferrets: (a–c): Stimulus-response plots showing the distribution of responses (ordinate) made by a ferret as a function of stimulus location in the horizontal plane (abscissa). The size of the dots indicates, for a given speaker angle, the proportion of responses made to different locations. Correct responses are those that fall on the diagonal line, whereas all other responses represent errors of different magnitude. Prior to occlusion of the left ear, the animal achieved 100% correct scores at all stimulus directions (a), but performed poorly, particularly on the side of the earplug, when the left ear was occluded (b). Further testing with the earplug still in place, however, led to a recovery in localization accuracy (c). (d) Mean change in performance (averaged across all speaker locations) over time in three groups of ferrets with unilateral earplugs. No change was found in trained ferrets (n = 3) that received an earplug for 6 weeks, but were tested only at the start and end of this period (circles and dashed regression line). Two other groups of animals received an equivalent amount of training while the left ear was occluded. Although the earplug was in place for less time, a much faster rate of improvement was observed in the animals that received daily training (n = 3; diamonds and solid regression line) compared to those that were tested every 6 days (n = 6; squares and dotted regression line). From Kacelnik et al. (2006).

Fig. 7

Plasticity of auditory localization depends on the auditory cortex. Change in performance (averaged across all speaker locations) over time in three groups of ferrets that received daily training with unilateral earplugs. Compared to the rapid and near complete recovery in localization accuracy observed in control animals (n = 3; black symbols and regression line), a significantly slower improvement was observed in animals in which A1 had been reversibly inactivated using muscimol-Elvax implants (n = 4; gray symbols and regression line). Moreover, no improvement in performance was observed in ferrets in which targeted apoptotic degeneration of corticocollicular neurons had been induced using a photoactivation technique (n = 3; open symbols and light gray regression line).

Fig. 8

Organization of the descending auditory corticocollicular projection in the ferret: (a) Retrogradely-labelled neurons were found in layer V across the entire extent of the ectosylvian gyrus following fluororuby (dextran tetramethylrhodamine) injections in the IC. Neurons were located in the shaded regions of auditory cortex shown in the insets. Scale bar = 1mm. (b) Projections originating in the primary cortical fields on the MEG target the lateral nucleus of the IC on the same side and the dorsal cortex and dorsal part of the central nucleus on both sides. Neurons in the secondary auditory cortical fields on the PEG have the same targets as those located in primary areas, but exclude the central nucleus. Neurons located in the AEG primarily innervate the tegmental midbrain. (c) Examples of anterograde labelling observed in different regions of the ipsilateral IC after an injection of fluororuby in the MEG. The terminal fields have a distinctive orientation in every IC subdivision. Scale bars = 100 μm. (Abbreviations: A1, primary auditory field; AEG, anterior ectosylvian gyrus; AAF, anterior auditory field; ADF, anterior dorsal field; AEG, anterior ectosylvian gyrus; AES, anterior ectosylvian area; AVF, anterior ventral field; CN, central nucleus of the IC; contra, contralateral to the injection site; Cn, cuneiform nucleus; D, dorsal; DC, dorsal cortex of the IC; ipsi, ipsilateral to the injection site; LL, lateral lemniscus; LN, lateral nucleus of the IC; M, medial; MEG, middle ectosylvian gyrus; PAG, periaqueductal gray; PEG,, posterior ectosylvian gyrus; Pn, pontine nuclei; PPF, posterior pseudosylvian field; PSF, posterior suprasylvian feld; VP, ventro-posterior area.) From Bajo et al. (2006a).