Sound localization behavior in ferrets: comparison of acoustic orientation and approach-to-target responses.

Auditory localization experiments typically either require subjects to judge the location of a sound source from a discrete set of response alternatives or involve measurements of the accuracy of orienting responses made toward the source location. To compare the results obtained by both methods, we trained ferrets by positive conditioning to stand on a platform at the center of a circular arena prior to stimulus presentation and then approach the source of a broadband noise burst delivered from 1 of 12 loudspeakers arranged at 30 degrees intervals in the horizontal plane. Animals were rewarded for making a correct choice. We also obtained a non-categorized measure of localization accuracy by recording head-orienting movements made during the first second following stimulus onset. The accuracy of the approach-to-target responses declined as the stimulus duration was reduced, particularly for lateral and posterior locations, although responses to sounds presented in the frontal region of space and directly behind the animal remained quite accurate. Head movements had a latency of approximately 200 ms and varied systematically in amplitude with stimulus direction. However, the final head bearing progressively undershot the target with increasing eccentricity and rarely exceeded 60 degrees to each side of the midline. In contrast to the approach-to-target responses, the accuracy of the head orienting responses did not change much with stimulus duration, suggesting that the improvement in percent correct scores with longer stimuli was due, at least in part, to re-sampling of the acoustical stimulus after the initial head turn had been made. Nevertheless, for incorrect trials, head orienting responses were more closely correlated with the direction approached by the animals than with the actual target direction, implying that at least part of the neural circuitry for translating sensory spatial signals into motor commands is shared by these two behaviors.

The projection from auditory cortex to cochlear nucleus in guinea pigs: an in vivo anatomical and in vitro electrophysiological study.

Previous anatomical experiments have demonstrated the existence of a direct, bilateral projection from the auditory cortex (AC) to the cochlear nucleus (CN). However, the precise relationship between the origin of the projection in the AC and the distribution of axon terminals in the CN is not known. Moreover, the influence of this projection on CN principal cells has not been studied before. The aim of the present study was two-fold. First, to extend the anatomical data by tracing anterogradely the distribution of cortical axons in the CN by means of restricted injections of biotinylated dextran amine (BDA) in physiologically characterized sites in the AC. Second, in an in vitro isolated whole brain preparation (IWB), to assess the effect of electrical stimulation of the AC on CN principal cells from which intracellular recordings were derived. BDA injections in the tonotopically organized primary auditory cortex and dorsocaudal auditory field at high and low best frequency (BF) sites resulted in a consistent axonal labeling in the ipsilateral CN of all injected animals. In addition, fewer labeled terminals were observed in the contralateral CN, but only in the animals subjected to injections in low BF region. The axon terminal fields consisting of boutons en passant or terminaux were found in the superficial granule cell layer and, to a smaller extent, in the three CN subdivisions. No axonal labeling was seen in the CN as result of BDA injection in the secondary auditory area (dorsocaudal belt). In the IWB, the effects of ipsilateral AC stimulation were tested in a population of 52 intracellulary recorded and stained CN principal neurons, distributed in the three CN subdivisions. Stimulation of the AC evoked slow late excitatory postsynaptic potentials (EPSPs) in only two cells located in the dorsal CN. The EPSPs were induced in a giant and a pyramidal cell at latencies of 20 ms and 33 ms, respectively, suggesting involvement of polysynaptic circuits. These findings are consistent with anatomical data showing sparse projections from the AC to the CN and indicate a limited modulatory action of the AC on CN principal cells.

c-Fos expression in the auditory pathways related to the significance of acoustic signals in rats performing a sensory-motor task.

Neuronal activity was established in the auditory pathways in relation to behavioural response and cognitive information processing during a sensory-motor acoustic learning. Rats were trained in three consecutive phases. The first phase was an association between an auditory stimulus and a food reward; the second phase a simple discrimination between two sounds of different frequency components, and the third phase a more complex discrimination involving both spectral and spatial sound dimensions. Auditory stimuli were bursts of complex sounds lasting 500 ms. Neuronal activity related to the behaviourally relevant stimuli was established in 20 "learning" rats undergoing this protocol, which were progressively sacrificed at the beginning, middle and end of each phase. For comparison, activity was also established in four "control" rats exposed to the same stimuli delivered pseudo-randomly, thus carrying no behavioural meaning. Neuronal activity was assessed immunocytochemically using the functional marker Fos. To establish a baseline, two rats were unexposed to controlled acoustic stimulation ("unstimulated" rats). In the superior olivary complex (SOC), inferior colliculus (IC) and medial geniculate body (MGB), the number of Fos-like immunopositive cells was comparable in "learning" and "control" animals, but higher than in the "unstimulated" rats. In the auditory cortex (AC), most prominently in the secondary area Te2, the number of Fos-like positive cells differed between "learning" and "control" rats, suggesting that the auditory cortical areas may be involved in the encoding of the behavioural significance of the acoustic stimuli.

Do auditory responses recorded from awake animals reflect the anatomical parcellation of the auditory thalamus?

Previous studies performed in anesthetized animals have shown differences between the acoustic responses of neurons recorded from the different divisions of the medial geniculate body (MGB). This study aimed at determining whether or not such differences are also expressed when neurons are recorded from awake animals. The auditory responses of 130 neurons of the auditory thalamus were determined in awake, restrained guinea pigs while the state of vigilance of the animals was continuously monitored. There were significantly more 'on' phasic evoked responses and significantly fewer 'non-responsive' or 'labile' cells in the ventral division of the MGB (MGv) than in the other divisions. The response latencies and the variability of the latencies were smaller in the MGv than in the other divisions. The tuning of the neurons obtained from MGv and from the lateral part of the posterior complex were significantly sharper than those coming from the dorsal division of the MGB and the medial division. The mean threshold and the percentage of monotonic vs. non-monotonic intensity functions were not different in the subdivisions of the auditory thalamus. When compared with previous studies, the quantifications of the acoustic responses obtained in the present study gave values that differed from those reported under deep anesthesia, but were close to those reported under light anesthesia. Lastly, even if none of the physiological characteristic makes it possible, by itself, to determine the locus of recordings in the auditory thalamus, we conclude that the physiological characteristics of the evoked responses obtained in MGv differ from those of other divisions.

Topographic organization of the dorsal nucleus of the lateral lemniscus in the cat.

The dorsal nucleus of the lateral lemniscus (DNLL) is an auditory structure of the brainstem. It plays an important role in binaural processing and sound localization and it provides the inferior colliculus with an inhibitory projection. The DNLL is a highly conserved auditory structure across mammals, but differences among species in its detailed organization have been reported. The main goal of this study was to analyze the topographic organization of the cat DNLL. Single, small iontophoretic injections of biotinylated dextran amine were made at different loci in the central nucleus of the inferior colliculus (CNIC). The distribution of the labeled structures in the ipsi- and contralateral DNLL was computer reconstructed in three dimensions. In individual sections, a band of labeling is seen in the DNLL on both sides. These two labeled bands occupy symmetric locations and are made of retrogradely labeled neurons with flattened dendritic arbors oriented parallel to each other. Moreover, the ipsilateral labeled band contains labeled terminal fibers parallel to the labeled dendrites. With three-dimensional reconstructions, it becomes evident that the labeled band seen in each individual DNLL section represents a slice through a rostrocaudally oriented lamina. The shape, size, orientation, and location of this lamina change as the injection site is shifted along the tonotopic axis of the CNIC. An injection in the low-frequency region of the CNIC, produces a lamina that resembles a flattened tube located in the dorsolateral corner of the DNLL. An injection in the high-frequency region of the CNIC, by contrast, results in a lamina that is an elongated sheet located at the ventromedial surface of the DNLL. The laminae of the DNLL might constitute the structural basis for its tonotopical organization. Previous studies (Merchan MA, et al. 1994. J Comp Neurol 342:259-278) in conjunction with our current results suggest that the laminar organization in the DNLL might be common among mammals.

Muscarinic activation of a non-selective cationic conductance in pyramidal neurons in rat basolateral amygdala.

In the present study, a cationic membrane conductance activated by the acetylcholine agonist carbachol was characterized in vitro in neurons of the basolateral amygdala. Extracellular perfusion of the K+ channel blockers Ba2+ and Cs+ or loading of cells with cesium acetate did not affect the carbachol-induced depolarization. Similarly, superfusion with low-Ca2+ solution plus Ba2+ and intracellular EGTA did not affect the carbachol-induced depolarization, suggesting a Ca2+-independent mechanism. On the other hand, the carbachol-induced depolarization was highly sensitive to changes in extracellular K+ or Na+. When the K+ concentration in the perfusion medium was increased from 4.7 to 10 mM, the response to carbachol increased in amplitude. In contrast, lowering the extracellular Na+ concentration from 143.2 to 29 mM abolished the response in a reversible manner. Results of coapplication of carbachol and atropine, pirenzepine or gallamine indicate that the carbachol-induced depolarization was mediated by muscarinic cholinergic receptors, but not the muscarinic receptor subtypes M1, M2 or M4, specifically. These data indicate that, in addition to the previously described reduction of a time- and voltage-independent K+ current (IKleak), a voltage- and time-dependent K+ current (IM), a slow Ca2+-activated K+ current (sIahp) and the activation of a hyperpolarization-activated inward rectifier K+ current (IQ), carbachol activated a Ca2+-independent non-selective cationic conductance that was highly sensitive to extracellular K+ and Na+ concentrations.

Preferential induction of fos-like immunoreactivity in granule cells of the cochlear nucleus by acoustic stimulation in behaving rats.

Neuronal activity in the cochlear nucleus was mapped in relation to acoustic stimuli that signalled a sensory-motor response, using Fos-like immunoreactivity. Rats were trained to associate an acoustic stimulus with a reward and then to discriminate between two sounds ('learning' rats; n = 18). The same stimuli carrying no behavioural significance were pseudo-randomly presented to 'control' rats (n = 4) to differentiate stimulus related- from learning related-activity. To establish a baseline, Fos-like immunoreactivity was determined in rats (n = 2) unexposed to acoustic stimulation. The number of Fos-positive cells was significantly increased in the rats exposed to sounds ('learning' and 'control') as compared to the non-stimulated animals. This stimulus related increase of Fos-like activity in the cochlear nucleus was most prominent in a subpopulation of small neurons, whose spatial distribution corresponds to that of the granule cells. There was also an increase in the number of Fos-positive neurons of larger size, but less prominent than for the small cells. Brief exposure to sounds (30 s) was sufficient to induce Fos-like activity.

Anatomic evidence of a three-dimensional mosaic pattern of tonotopic organization in the ventral complex of the lateral lemniscus in cat.

The ventral complex of the lateral lemniscus (VCLL, i.e., the ventral and intermediate nuclei) is composed of cells embedded in the fibers of the lateral lemniscus. These cells are involved in the processing of monaural information and receive input from the collaterals of the fibers ascending to the inferior colliculus. Whereas tonotopic organization is a feature of all other nuclei of the auditory system, this functional principle is debated in the VCLL. We have made focal injections of the tracer biotinylated dextran amine into different frequency band representations of the inferior colliculus in cat. Retrogradely labeled cells and terminal fibers (collaterals of efferent local axons and other ascending lemniscal fibers) were found in the ipsilateral VCLL. The spatial distribution of the labeling was analyzed using three-dimensional (3-D) reconstruction and computer graphical visualization techniques. A complex topographic organization was found. In all cases, labeled fibers and cells were distributed in multiple clusters throughout the dorsoventral extent of the VCLL. The shape, size, and location of the labeled clusters suggest an interdigitation of clusters assigned to different frequency-band representations. But an overall mediolateral distribution gradient was observed, with high frequencies represented medially and lower frequencies progressively more laterally. We conclude that the clusters may represent discontinuous frequency-band compartments as a counterpart to the continuous laminar compartments in the remaining auditory nuclei. The 3-D orderly mosaic pattern indicates that the VCLL preserves the spectral decomposition originated in the cochlea in a way that facilitates across-frequency integration.

Discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus of the rat.

The aim of the present study was to characterize the discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the rat. In the absence of acoustic stimulation, two types of spontaneous discharge patterns were observed: units tended to fire in a bursting or in a nonbursting mode. The distribution of units in the DNLL based on spontaneous firing rate followed a rostrocaudal gradient: units with high spontaneous rates were most commonly located in the rostral part of the DNLL, whereas in the caudal part units had lower spontaneous discharge rates. The most common response pattern of DNLL units to 200 ms binaural noise bursts contained a prominent onset response followed by a lower but steady-state response and an inhibitory response in the early-off period. Thresholds of response to noise bursts were on average higher for DNLL units than for units recorded in the inferior colliculus under the same experimental conditions. The DNLL units were arranged according to a mediolateral sensitivity gradient with the lowest threshold units in the most lateral part of the nucleus. In the rat, as in other mammals, the most common DNLL binaural input type was an excitatory response to contralateral ear stimulation and inhibitory response to ipsilateral ear stimulation (EI type). Pure tone bursts were in general a more effective stimulus compared to noise bursts. Best frequency (BF) was established for 97 DNLL units and plotted according to their spatial location. The DNLL exhibits a loose tonotopic organization, where there is a concentric pattern with high BF units located in the most dorsal and ventral parts of the DNLL and lower BF units in the middle part of the nucleus.

Single unit activity in the inferior colliculus of the rat elicited by electrical stimulation of the cochlea.

The activity of single neurons (n = 182) of the central nucleus of the inferior colliculus (CIC) of the rat was recorded in response to unilateral electrical stimulation of the left cochlea and/or acoustical stimulation of the right ear. The probability of response to both modes of stimulation was comparable (90 per cent for contralateral and 60 per cent for ipsilateral presentation). Response patterns consisted predominantly of onset excitations. Response latencies to electrical stimuli ranged from 3 to 21 ms, with an average value of 9.7 ms (SD = 3.5 ms) in the ipsilateral CIC and 6.6 ms (SD = 3.4 ms) in the contralateral CIC. With respect to binaural inputs, the majority of units were excited by stimulation of either ear (EE; about 60 per cent) while about one third were influenced by one ear only (EO). Units excited by one ear and inhibited by the other (EI) were rare. The main difference between the present implanted rats and normal animals was the virtual absence here of inhibitory effects for both types of stimuli when they were delivered to the ipsilateral ear (very few EI units).

Morphology and spatial distribution of corticothalamic terminals originating from the cat auditory cortex.

In this paper we studied the morphology and spatial distribution of corticothalamic axons and terminals originating from the auditory cortical fields of the cat. The anterograde tracer biocytin was injected at electrophysiologically characterized loci in the primary (AI) (N = 2), anterior (AAF) (N = 1), posterior (PAF) (N = 1) and secondary (AII) (N = 2) auditory fields. In all cases, two different types of labeled terminals were found in the auditory thalamus: small spherical endings (1-2 microns) and giant, finger-like endings (5-10 microns). After biocytin injections in AI and AAF, the majority of anterogradely labeled axons terminated in the rostral half of the pars lateralis (LV) of the ventral division of the medial geniculate body (vMGB). In LV, the corticothalamic axons ramified profusely, giving rise to dense terminal fields forming well delineated curved stripes, with small spherical endings. Additional terminal fields formed by small endings were observed in the medial division of the medial geniculate body (mMGB). Giant endings were observed in a small area in the dorsal nucleus (D) of the dorsal division of the medial geniculate body (dMGB), near its border with the vMGB. PAF projections were located in the caudal half of vMGB and in mMGB, where only small terminals were found. Giant endings were seen in the superficial part of dMGB emerging from labeled corticothalamic axons oriented in parallel to the dorsal surface of the MGB. Projections from AII gave rise to a main terminal field of small endings in D; a second terminal field consisting of giant endings intermingled with small endings was found in the deep dorsal nucleus (DD) of dMGB. We conclude that small terminals serve the feedback projection to the thalamic nucleus from which the injected cortical field receives its main input, whereas giant terminals cross the borders between the parallel ascending auditory pathways.

The auditory pathway in cat corpus callosum.

The cortical auditory fields of the two hemispheres are interconnected via the corpus callosum. We have investigated the topographical arrangement of auditory callosal axons in the cat. Following circumscribed biocytin injections in the primary (AI), secondary (AII), anterior (AAF) and posterior (PAF) auditory fields, labelled axons have been found in the posterior two-thirds of the corpus callosum. Callosal axons labelled by small individual cortical injections did not form a tight bundle at the callosal midsagittal plane but spread over as much as one-third of the corpus callosum. Axons originating from different auditory fields were roughly topographically ordered, reflecting to some extent the rostro-caudal position of the field of origin. Axons from AAF crossed on average more rostrally than axons from AI; the latter crossed more rostrally than axons from PAF and AII. Callosal axons originating in a discrete part of the cortex travelled first in a relatively tight bundle to the telo-diencephalic junction and then dispersed progressively. In conclusion, the cat corpus callosum does not contain a sector reserved for auditory axons, nor a strictly topographically ordered auditory pathway. This observation is of relevance to neuropsychological and neuropathological observations in man.

Neuronal morphology and efferent projections of the dorsal nucleus of the lateral lemniscus in the rat.

The dorsal nucleus of the lateral lemniscus (DLL) is the main source of inhibitory influence in the auditory brainstem of mammals. The cytoarchitecture and connectional properties of DLL were established in the cat in contrast to the rat. The goal of the present study was to establish to what extent the anatomical properties of the rat DLL compare to those of the cat, thus providing a basis of interpretation for future functional studies in the rat, an animal model used more and more in the auditory system. DLL of the rat contains four well-differentiated neuronal types, as seen in Nissl-stained material. Type I neurons are large and multipolar with abundant cytoplasm and darkly stained Nissl substance. Type II neurons are large, bipolar and darkly stained in Nissl material. Type III neurons are medium in size and their soma is round or ovoid. Type IV neurons are small and round with scant cytoplasm; they seem to be also the least common neuronal type of the DLL. After Phaseolus vulgaris-leucoagglutinin or biocytin injections in the DLL, fibers and terminals labeled by orthograde transport were observed in the corresponding region of the contralateral DLL and in the inferior colliculus, bilaterally. A few labeled fibers and terminal fields were seen in the deep layers of the superior colliculus bilaterally, as well as in the medial division of the medial geniculate body and, even more rostrally, in the posterior nucleus of the thalamus. Descending projections from DLL terminated in the periolivary regions of the ipsilateral superior olivary complex. Retrograde tracing based on injections of horseradish peroxidase in the various targets of the DLL confirmed the connections established with orthograde labeling.