No abstract

Insulin-like growth factor-1 (IGF-1) has been shown to play a key role during embryonic and postnatal development of the CNS, but its effect on a sensory organ has not been studied in vivo. Therefore, we examined cochlear growth, differentiation, and maturation in Igf-1 gene knock-out mice at postnatal days 5 (P5), P8, and P20 by using stereological methods and immunohistochemistry. Mutant mice showed reduction in size of the cochlea and cochlear ganglion. An immature tectorial membrane and a significant decrease in the number and size of auditory neurons were also evident at P20. IGF-1-deficient cochlear neurons showed increased caspase-3-mediated apoptosis, along with aberrant expression of the early neural markers nestin and Islet 1/2. Cochlear ganglion and fibers innervating the sensory cells of the organ of Corti presented decreased levels of neurofilament and myelin P(0) in P20 mouse mutants. In addition, an abnormal synaptophysin expression in the somata of cochlear ganglion neurons and sensory hair cells suggested the persistence of an immature pattern of synapses distribution in the organ of Corti of these animals. These results demonstrate that lack of IGF-1 in mice severely affects postnatal survival, differentiation, and maturation of the cochlear ganglion cells and causes abnormal innervation of the sensory cells in the organ of Corti.

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Monaural spectral features due to pinna diffraction are the primary cues for elevation. Because these features appear above 3 kHz where the wavelength becomes comparable to pinna size, it is generally believed that accurate elevation estimation requires wideband sources. However, psychoacoustic tests show that subjects can estimate elevation for low-frequency sources. In the experiments reported, random noise bursts low-pass filtered to 3 kHz were processed with individualized head-related transfer functions (HRTFs), and six subjects were asked to report the elevation angle around four cones of confusion. The accuracy in estimating elevation was degraded when compared to a baseline test with wideband stimuli. The reduction in performance was a function of azimuth and was highest in the median plane. However, when the source was located away from the median plane, subjects were able to estimate elevation, often with surprisingly good accuracy. Analysis of the HRTFs reveals the existence of elevation-dependent features at low frequencies. The physical origin of the low-frequency features is attributed primarily to head diffraction and torso reflections. It is shown that simple geometrical approximations and models of the head and torso explain these low-frequency features and the corresponding elevations cues.

Stereological methods were employed to estimate the volume and neuron numbers of the rat dorsal column nuclei (DCN). These methods were applied to Nissl-stained sections from control animals and cases that received injections of horseradish peroxidase in the thalamus, the cerebellum, or the spinal cord. Additional cases received combinations of fluorescent tracers in the same structures, to examine whether some of the retrogradely labeled neurons sent collaterals to different targets. The mean volume of the DCN is 0.81 mm(3) (range 0.65-1.10 mm(3)), of which 3%, 39%, and 59% correspond, respectively, to the nucleus of Bischoff (Bi), the gracile (Gr), and the cuneate (Cu) nuclei. Within Cu, the middle division (CuM) is the largest (42%), followed by the rostral (CuR; 36%) and caudal (CuC; 22%) divisions. The mean total number of neurons in the DCN is 16,000 (range 12,400-19,500), of which 2.4%, 34.0% and 63.6% correspond, respectively, to Bi, Gr, and Cu. Within Cu, CuM contains 48% of all neurons, and 27% correspond to CuR and 25% to CuC. Interanimal variability is moderate for the whole DCN and Cu but increases when individual nuclei are considered. About 80% of DCN neurons project to the thalamus, 3% to the spinal cord, and 7% to the cerebellum. Thalamic-projecting cells are more numerous in CuM and Gr (83%), and relatively less common in Bi and CuC (72-74%). Most of the DCN neurons projecting to the spinal cord appear in CuC and CuM. Two-thirds of the neurons projecting to the cerebellum are located in CuR, 20% in CuM, and 15% in Gr. A small fraction of neurons projects simultaneously to spinal cord and thalamus.