Electrically induced Fos-like immunoreactivity in the auditory pathway of the rat: Effects of survival time, duration, and intensity of stimulation (original) (raw)
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Neuroscience Research, 1994
Fos-like immunoreactivity (FLI) was mapped in the auditory pathway of Sprague-Dawley rats in response to unilateral electrical stimulation of the cochlea implanted with two stimulating electrodes. Densely packed FLI neurons were widely distributed in the dorsal cochlear nucleus (more ipsilaterally than contralaterally), while FLI neurons were rare in the posteroventral cochlear nucleus and virtually absent in the anteroventral cochlear nucleus. Sparse FLI was detected in the superior olivary complex, the pontine nuclei and the ipsilateral dorsal nucleus of the lateral lemniscus, whereas the contralateral dorsal nucleus of the lateral lemniscus was moderately labeled. In the inferior colliculus, the pattern of FLI was similar on both sides, restricted mainly to its dorsal and external cortices. At the thalamic level, FLI neurons were seen in the dorsal and medial divisions of the medial geniculate body as well as in the peripeduncular nucleus. A significant increase of FLI was observed in the temporal cortex. This study demonstrates the presence of selective functional changes along the auditory pathway elicited by electrical stimulation of the cochlea, as revealed by FLI.
Neuroscience Letters, 1999
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.
Hearing Research, 2001
The pattern of c-Fos expression was mapped in the adult rat's brain following unilateral cochlear lesions. In normal and cochlear lesioned rats, c-Fos expression was induced with sound stimuli. Acoustic stimulation consisted of pulses of four tones. An additional control group consisted of non-stimulated rats. In the cochlear nuclei (CN), c-Fos activation was scarce in isolated rats and increased strongly following sound stimulation. Following unilateral cochlear lesion, acoustically driven expression was decreased in all CN in both the lesioned and the untreated sides. The ventromedial periolivary nucleus and the rostral periolivary nucleus showed c-Fos activation in isolated conditions and were strongly activated following sound stimulation. The rest of the superior olivary complex showed no c-Fos activation in isolated rats and a weak activation following sound stimulation. Following unilateral cochlear lesions, acoustically driven expression was decreased in some, but not all superior olivary nuclei in both the lesioned and the untreated sides. In the lateral lemniscus complex, c-Fos activation was scarce in isolated rats and increased strongly after stimulation. Following unilateral cochlear lesion, acoustically driven expression decreased bilaterally in all nuclei. We have found that unilateral inner ear lesions lead to bilateral impairment of the capability of acoustic pathway neurons, to being c-Fos-activated following sound stimulation. ß periolivary nuclei; VCA, anterior ventral cochlear nucleus; VCP, posterior ventral cochlear nucleus; DC, dorsal cochlear nucleus; DLL, dorsal nucleus of the lateral lemniscus; DPO, dorsal periolivary nuclei; GrC, granular cell layer; IC, inferior colliculus; ILL, intermediate nucleus of the lateral lemniscus; LL, nuclei of the lateral lemniscus; LSO, lateral superior olive; LVPO, ventrolateral periolivary nuclei; MSO, medial superior olive; MVPO, ventromedial periolivary nuclei; RPO, rostral periolivary region; SOC, superior olivary complex; SPO, superior paraolivary nucleus; Tz, trapezoid body nucleus; VLL, ventral nucleus lateral lemniscus; VPO, ventral periolivary nuclei Hearing Research 162 (2001) 53^66 www.elsevier.com/locate/heares
Mechanisms contributing to central excitability changes during hearing loss
Exposure to loud sound causes cochlear damage resulting in hearing loss and tinnitus. Tinnitus has been related to hyperactivity in the central auditory pathway occurring weeks after loud sound exposure. However, central excitability changes concomitant to hearing loss and preceding those periods of hyperactivity, remain poorly explored. Here we investigate mechanisms contributing to excitability changes in the dorsal cochlear nucleus (DCN) shortly after exposure to loud sound that produces hearing loss. We show that acoustic overexposure alters synaptic transmission originating from the auditory and the multisensory pathway within the DCN in different ways. A reduction in the number of myelinated auditory nerve fibers leads to a reduced maximal firing rate of DCN principal cells, which cannot be restored by increasing auditory nerve fiber recruitment. In contrast, a decreased membrane resistance of DCN granule cells (multisensory inputs) leads to a reduced maximal firing rate of DCN principal cells that is overcome when additional multisensory fibers are recruited. Furthermore, gain modulation by inhibitory synaptic transmission is disabled in both auditory and multisensory pathways. These cellular mechanisms that contribute to decreased cellular excitability in the central auditory pathway are likely to represent early neurobiological markers of hearing loss and may suggest interventions to delay or stop the development of hyperactivity that has been associated with tinnitus. auditory brainstem | fusiform cell | parallel fiber | deafness | whole-cell patch I t is well established that exposure to loud sound causes damage to the cochlea and results in an elevation of hearing thresholds (1) often accompanied by a reduction of auditory nerve (AN) firing rate (2-4). Although peripheral cellular mechanisms contributing to hearing loss have been thoroughly described (5-11), mechanisms in the central auditory system involved in the early stages of hearing loss following acoustic overexposure (AOE) are poorly understood. The dorsal cochlear nucleus (DCN) is one of the first relays within the central auditory pathway (12). Hyperactivity in the DCN has been reported weeks after AOE in vivo and in brain slices and has been correlated with tinnitus (13-15). Our recent study showed the presence of bursts in DCN fusiform cells (FCs) just a few days after AOE (16). Therefore, the aim of the current study was to investigate synaptic transmission at this early time point after AOE and determine whether changes in auditory or multisensory (MS) inputs to FCs might contribute to the altered excitability in the DCN. We postulate that changes following AOE could represent the earliest modifications of the central auditory pathway preceding the later development of DCN hyperactivity and tinnitus. DCN FCs integrate the acoustic information from AN fibers with MS signals transmitted via granule cell axons (parallel fibers) (17-19). DCN granule cells and their parallel fiber axons represent a site of integration of multimodal sensory inputs such as the trigeminal ganglion (20), the spinal trigeminal nucleus (21), the pontine nucleus (22), the cuneate nucleus, the gracile nuclei (23, 24), and the raphe nucleus (25). These inputs are likely to encode proprioceptive information on the position of the ears relative to the sound source (26) and/or the suppression of body-generated sounds or vocal feedback (17, 27, 28). Responses of FCs are further shaped by feed-forward inhibition, mainly through in-hibitory tuberculo-ventral cells activated by AN fibers and cart-wheel cells activated by parallel fibers (17, 29-31). Consequently, the changes in intrinsic excitability and spontaneous activity of FCs following AOE (16) may arise as a consequence of specific changes occurring along the AN and the MS pathway after AOE. The way in which a neuron processes signals can be captured by its transfer function or its input-output relationship (32). Modulation of ex-citability changes the shape of this relationship, thereby affecting either the slope (or gain) or its maximum (33-35). We therefore used FC transfer functions to target central excitability changes after AOE. Our experimental and computational modeling studies show that synaptic excitability is down-regulated in FCs during hearing loss, at the early stages following AOE, and that the underlying cellular mechanisms are specific to the AN and MS synaptic inputs. Results Acoustic Overexposure Induces Hearing Threshold Elevations and Decreases FC Excitability. We assessed the effects of AOE on auditory brainstem responses (ABR) for frequencies varying from 8 to 30 kHz. Wistar rats aged 15-18 d were subjected to 110 dB sound pressure level (SPL), 14.8 kHz for 4 h, and ABR were recorded 3-4 d later. There were no changes in ABR threshold and latencies measured at day 0 and day 3-4 in control animals (Fig. S1C and Table S1). We found that shifts of hearing thresholds of 20-30 dB SPL were observed for frequencies above the frequency used during the AOE protocol (Fig. S1 A-C) whereas wave 1 and 2 latencies were unaffected (Tables S2 and S3). ABR threshold shifts were temporary as they recovered after 3 mo (Fig. S1C). Whole-cell current clamp recordings from DCN FCs in vitro were then performed at a similar time (3-4 d) after AOE or after a sham procedure with anesthesia only (un-exposed). Excitatory post-synaptic potentials (EPSPs) and action potentials (APs) could be elicited in FCs after stimulating the AN in the DCN deep layer (19, 36, 37) (SI Methods and Fig. 1 A-C) or MS inputs in the DCN molecular layer (37, 38) (Fig. 1 D-F). AOE led to reduction of the EPSPs evoked by AN and MS input stimulations [from 8 ± 1 mV (n = 5) to 4 ± 1 mV (n = 6) in unexposed conditions and after AOE, respectively (P < 0.01, unpaired t test) (Fig. 1B) and from 6 ± 1 mV (n = 8) to 1.5 ± 0.5 mV (n = 6) in unexposed conditions and AOE, respectively (P < Author contributions: M.H. designed research; N.P. and M.B. performed research; M.J.I., M.M., and J.M. contributed new reagents/analytic tools; N.P., M.J.I., and M.B. analyzed data; and N.P., C.H.L., I.D.F., and M.H. wrote the paper. The authors declare no conflict of interest.
Excitability of auditory neurons in the dorsal and ventral cochlear nuclei of and mice☆
Experimental Neurology, 1984
Extracelhdar response properties were studied in neurons of the dorsal and ventral divisions of the cochlear nucleus (DCN and VCN, respectively) of DBA/2 (DBA) and C57BL/6 (C57) mice. Mice of the former inbred strain show msceptibility to audiogenic seixurcs and have severe high frequency hearing loss when young; mice of the latter strain do not. Whereas a%dischatBes had been readiIy observed in the inferior colliculm of DBA mice in a previous study, they were never observed in the cochlear nucleus. The incidence of nonmonotonic intensity functions, the slopes of intensity functions, and the incidence of inhibition in msponse areas indicated that inhibition was diminished in the DCN of DBA mice. However, in the VCN, these response properties did not differ between the two strains. Them appeared to be an "amplification" of excitability (i.e., attenuation of inhibition) from VCN to DCN to inferior colliculus in DBA mice.
Pathways from auditory cortex to the cochlear nucleus in guinea pigs
The inferior colliculus (IC) and superior olivary complex (SOC) are important sources of descending pathways to the cochlear nucleus. The IC and SOC are also targets of direct projections from the auditory cortex but it is not known if cortical axons contact the cells that project to the cochlear nucleus. Multi-labeling techniques were used to address this question in guinea pigs. A fluorescent anterograde tracer was injected into temporal cortex to label corticofugal axons. Different fluorescent tracers were injected into one or both cochlear nuclei to label olivary and collicular cells. The brain was subsequently processed for fluorescence microscopy and the IC and SOC were examined for apparent contacts between cortical axons and retrogradely labeled cells. The results suggest that cortical axons contact cochlear nucleus-projecting cells in both IC and SOC. In both regions, contacts were more numerous on the side ipsilateral to the injected cortex. In the IC, the contacted cells projected ipsilaterally or contralaterally to the CN. In the SOC, the contacted cells projected ipsilaterally, contralaterally or bilaterally to the CN. We conclude that auditory cortex is in a position to modulate descending pathways from both the IC and SOC to the cochlear nucleus.
The response properties of neurons in different fields of the auditory cortex in the rat
Hearing Research, 2013
The auditory cortex (AC) of the rat has been the subject of many studies, yet the details of its functional organization are still not well understood. We describe here the functional organization of the AC in young rats (strain Long Evans, aged 30e35 days, anesthetized with ketamine/xylazine) on the basis of the neuronal responses to acoustic stimuli. Based on the neuronal responses to broad band noise (BBN) and pure tone bursts, the AC may be divided into the primary auditory cortex (AI) and three other core fields: anterior (AAF), suprarhinal (SRAF) and posterior (PAF) as well as an unspecific region (UR) inserted between the AI and AAF. The core fields are surrounded by a belt area. Neurons in the AI, AAF, SRAF and PAF showed well defined characteristic frequencies (CF) in response to pure tone stimulation; in contrast, UR neurons responded only at high intensities without a clear CF. Neurons responding only to BBN stimulation were found mostly in the belt area. The putative borders between the core fields were determined by changes in their tonotopic gradient; however, no tonotopic organization was found in the PAF. Neurons with the shortest response latencies to BBN stimulation were found in layer 4 (L4) and layer 6 (L6) in the AI, while those with the longest latencies in the superficial layers (L1/2) of the belt area. Similar principles of responsiveness were observed when the spike rate in response to BBN stimulation was evaluated, with the highest rate present in L4 of the AI and the lowest in L1/2 of the belt area. According to the shape of the peristimulus time histograms, the responses of neurons in the AC of the rat may be classified as pure onset, sustained, onset-sustained, double peak or late onset. The most dominant in all fields, as well as in all layers, was the pure onset response. Our findings offer further cues for understanding the functional organization of the AC in the rat.
2002
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