François de Ribaupierre

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.

Projections of the reticular complex of the thalamus onto physiologically characterized regions of the medial geniculate body

Afferents from the reticular complex of the thalamus (RE) to the subdivisions of the medial geniculate body (MGB) in the cat were studied by retrograde axonal transport of horseradish peroxidase injected in sites where single unit responses to tones had been characterized. All MGB subdivisions studied received afferents from the same region of RE corresponding to its ventral posterior third, characterized by large neurons. No obvious differences were seen in the localization of labelled neurons within RE according to which MGB subdivision was injected, except that pars lateralis afferents seemed to originate from somewhat more limited portions of RE.

Notch/Notch ligands and Math1 expression patterns in the organ of Corti of wild-type and Hes1 and Hes5 mutant mice.

The sensory epithelium of the mammalian cochlea (the organ of Corti) represents an excellent developmental system. The organ of Corti contains two main cell types: the sensory hair cells and the supporting cells which are organized in a defined mosaic pattern. Previous results have demonstrated the participation of Notch signaling in the regulation of the pattern of hair cell differentiation within this sensory mosaic. It has also been shown that the basic helix-loop-helix (bHLH) transcription factor Math1 is a positive regulator of hair cell differentiation. We demonstrated that Hes1 and Hes5, two members of the inhibitory bHLH transcription factors, act as negative regulators of hair cell differentiation. Loss-of-function studies implicating the neurogenic genes Notch1, Jag2, Hes1 and Hes5 generated a significant increase in the number of hair cells. However, their functional interplay within the organ of Corti has not been determined. To clarify the mechanisms that regulate hair cell differentiation, we examined the expression of Notch/Notch ligand system and Math1 in the developing organ of Corti of Hes1- and Hes5-deficient mice. Our study suggests complex specific relationships between Notch signaling, Math1 and Hes1/Hes5 in the control of hair cell differentiation in the developing organ of Corti.

Corticofugal modulation of functional connectivity within the auditory thalamus of rat, guinea pig and cat revealed by cooling deactivation

Microelectrode recordings were simultaneously performed at multiple sites in the medial geniculate body (MGB) of anesthetized cats, rats and guinea pigs. We studied the effect of cortical deactivation on the association of neural activity within the thalamus during spontaneous activity. The corticofugal influence was suppressed by temporary cooling of the auditory cortex. Pairs of spike trains recorded from the same electrode were distinguished from cases where units were in MGB but recorded with different electrodes. Time domain analyses included crosscorrelations and search for precise repetition of complex spatiotemporal firing patterns of reverberating thalamic circuits. As a complementary approach we performed bispectral analyses of simultaneously recorded local field potentials in order to uncover the frequency components of their power spectra which are non linearly coupled. All results suggest that new functional neuronal circuits might appear at the thalamic level in the absence of input from the cortex. The newly active intrathalamic connections would provide the necessary input to sustain the reverberating activity of thalamic cell assemblies and generate low frequency non-linear interactions. The dynamic control exerted by the cortex over the functional segregation of information processing carried out in the thalamus conforms with theoretical neural network studies and with the functional selectivity-adaptive filtering theory of thalamic neuronal assemblies. Although this general conclusion remains valid across species, specific differences are discussed in the frame of known differences of the microcircuitry elements.

NON-VERBAL AUDITORY RECOGNITION IN NORMAL SUBJECTS AND BRAIN-DAMAGED PATIENTS : EVIDENCE FOR PARALLEL PROCESSING

Three different aptitudes involved in sound object recognition were tested in 60 normal subjects and 20 brain-damaged patients: (i) capacity to segregate sound objects on different cues (intensity steps, coherent temporal modulations or signal onset synchrony); (ii) asemantic recognition of sounds of real objects by judging whether two different sound samples belonged to the same object; and (iii) semantic identification of sounds of real objects as judged by means of a multiple choice response test. In 12 patients, different aptitudes involved in auditory recognition were disrupted separately and in a way which speaks in favour of parallel rather than hierarchical processing. There was no strong association between deficits in non-verbal auditory recognition and aphasia or the side of lesion.

Neuronal organization of the stapedius reflex pathways in the rat: a retrograde HRP and viral transneuronal tracing study

The location of stapedius motoneurons in the rat was determined with horseradish peroxidase (HRP) retrograde tracing techniques. After injection of free HRP or wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the stapedius muscle on one side, labeled neurons were seen ipsilaterally in a region ventromedial to the rostral half of the facial motor nucleus (VII), extending rostrally to the caudal part of the superior olivary complex (SOC). These labeled neurons, located outside the SOC and facial motor nuclei themselves, constitute the pool of stapedius motoneurons, in agreement with previous descriptions for other species. In order to identify the origin of some inputs to the stapedius motoneurons, injections of herpes virus suis were performed in the stapedius muscle. After replication in the motoneurons, the viruses are transported transneuronally to some premotor neurons, as previously reported in other systems. The presence of the virus was detected by immunofluorescence in neurons corresponding to the stapedius motoneurons labeled with HRP or WGA-HRP. In addition, infected neurons were seen bilaterally at the level of the SOC, in the mediotrapezoid region, where no labeled cells were observed following HRP or WGA-HRP injections in the stapedius muscle. These neurons were considered as infected transneuronally and therefore providing inputs to the pool of stapedius motoneurons. No virus could be detected in cochlear nucleus neurons. These data are consistent with previous observations in the rabbit based on lesion experiments, suggesting that neurons at the level of the SOC are involved in the reflex arc of middle ear muscles.

Tensor tympani reflex pathways studied with retrograde horseradish peroxidase and transneuronal viral tracing techniques

The neural pathway involved in activation of the tensor tympani (TT) muscle was studied in the rat using retrograde HRP and transneuronal viral tracing techniques. The pool of TT motoneurons labeled with HRP was located ipsilaterally under the anterior third of the trigeminal motor nucleus and extended rostrally towards the lateral lemniscus. The origin of the inputs to these motoneurons was then determined using transneuronal viral transport: presumably transneuronally infected neurons appeared bilaterally in the vicinity of the superior olivary complex, mainly in between the two nuclei of the trapezoid body. The present data are consistent with previous conclusions based on lesion experiments that the TT reflex loop is made up of a chain of 4 neurons.

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.

Arborization of corticothalamic axons in the auditory thalamus of the cat: A PHA-L tracing study

As a result of Phaseolus vulgaris leucoagglutinin (PHA-L) injection in the primary auditory cortex of the cat, portions of corticofugal axons could be traced individually in the reticular complex of the thalamus (RE) and in the medial geniculate body (MGB). On their way to the MGB, axons were seen to give off collaterals which terminated in RE. In the MGB, an individual corticofugal axon was fully reconstructed. It ramified at 3 distinct frontal levels in the rostral half of the pars lateralis (LV). Its terminal branches gave rise to boutons en passant and terminaux in a stripe of LV (parallel to the isofrequency contours), overlapping a cluster of retrogradely labeled neurons, supporting at the microscopic level the principle of the reciprocity of thalamocortical and corticothalamic projections.

Several neuronal and axonal types form long intrinsic connections in the cat primary auditory cortical field (AI)

Intrinsic connections in the cat primary auditory field (AI) as revealed by injections Phaseolus vulgaris leucoagglutinin (PHA-L) or biocytin, had an anisotropic and patchy distribution. Neurons, labelled retrogradely with PHA-L were concentrated along a dorsoventral stripe through the injection site and rostral to it; the spread of rostrally located neurons was greater after injections into regions of low rather than high characteristic frequencies. The intensity of retrograde labelling varied from weak and granular to very strong and Golgi-like. Out of 313 Golgi like retrogradely labelled neurons 79.6% were pyramidal, 17.2% multipolar, 2.6% bipolar, and 0.6% bitufted; 13.4% were putatively inhibitory, i.e. aspiny or sparsely spiny multipolar, or bitufted. Individual anterogradely labelled intrinsic axons were reconstructed for distances of 2 to 7 mm. Five main types were distinguished on the basis of the branching pattern and the location of synaptic specialisations. Type 1 axons travelled horizontally within layers II to VI and sent collaterals at regular intervals; boutons were only present in the terminal arborizations of these collaterals. Type 2 axons also travelled horizontally within layers II to VI and had rather short and thin collateral branches; boutons or spine-like protrusions occurred in most parts of the axon. Type 3 axons travelled obliquely through the cortex and formed a single terminal arborization, the only site where boutons were found. Type 4 axons travelled for some distance in layer I; they formed a heterogeneous group as to their collaterals and synaptic specializations. Type 5 axons travelled at the interface between layer VI and the white matter; boutons en passant, spine-like protrusions, and thin short branches with boutons en passant were frequent all along their trajectory. Thus, only some axonal types sustain the patchy pattern of intrinsic connectivity, whereas others are involved in a more diffuse connectivity.