Publications using TDT

The circadian oscillator in the suprachiasmatic nucleus (SCN) is entrained to the environmental light/dark cycle through photic information conveyed from the retina. The vast majority of projections to the SCN arise from melanopsin-expressing ganglion cells that are intrinsically light sensitive and that receive inputs from both rods and cones. To investigate the relative contributions of the different photoreceptive systems in shaping the photic signal influencing the circadian clock, we analyzed neuronal responses of single SCN neurons using extracellular electrophysiological recordings under different conditions of light adaptation. In the majority of neurons (78%), the spike rate is increased by light stimulation whereas the remainder are light-inhibited. The neuronal response to light is composed of several components distinguished by their temporal dynamics and degree of alteration after previous light exposure. SCN neurons display a sustained response to light followed by persistence of the response after light offset. These responses are sluggish and relatively unaffected by previous light exposures. Neurons also respond with a brisk, excitatory ON response and often an OFF response that is either excitatory or inhibitory. ON–OFF responses are transient and strongly reduced by previous bright white light exposure. Furthermore, two types of neuronal response patterns can be distinguished by the presence or absence of a slow-transient component that follows the transient ON response. The transient ON–OFF components express light adaptation properties characteristic of retinal channels involving cones, whereas the sustained and persistent components are consistent with in vitro response properties reported for melanopsin-expressing ganglion cells.

Space-specific neurons in the barn owl's auditory space map gain spatial selectivity through tuning to combinations of the interaural time difference (ITD) and interaural level difference (ILD). The combination of ITD and ILD in the subthreshold responses of space-specific neurons in the external nucleus of the inferior colliculus (ICx) is well described by a multiplication of ITD- and ILD-dependent components. It is unknown, however, how ITD and ILD are combined at the site of ITD and ILD convergence in the lateral shell of the central nucleus of the inferior colliculus (ICcl) and therefore whether ICx is the first site in the auditory pathway where multiplicative tuning to ITD- and ILD-dependent signals occurs. We used extracellular recording of single neurons to determine how ITD and ILD are combined in ICcl of the anesthetized barn owl ( Tyto alba). A comparison of additive, multiplicative, and linear-threshold models of neural responses shows that ITD and ILD are combined nonlinearly in ICcl, but the interaction of ITD and ILD is not uniformly multiplicative over the sample. A subset (61%) of the neural responses is well described by the multiplicative model, indicating that ICcl is the first site where multiplicative tuning to ITD- and ILD-dependent signals occurs. ICx, however, is the first site where multiplicative tuning is observed consistently. A network model shows that a linear combination of ICcl responses to ITD–ILD pairs is sufficient to produce the multiplicative subthreshold responses to ITD and ILD seen in ICx.

Although the auditory cortex is known to be essential for normal sound localization in the horizontal plane, its contribution to vertical localization has not so far been examined. In this study, we measured the acuity with which ferrets could discriminate between two speakers in the midsagittal plane before and after silencing activity bilaterally in the primary auditory cortex (A1). This was achieved either by subdural placement of Elvax implants containing the GABA A receptor agonist muscimol or by making aspiration lesions after determining the approximate location of A1 electrophysiologically. Psychometric functions and minimum audible angles were measured in the upper hemifield for 500-, 200-, and 40-ms noise bursts. Muscimol-Elvax inactivation of A1 produced a small but significant deficit in the animals’ ability to localize brief (40-ms) sounds, which was reversed after removal of the Elvax implants. A similar deficit in vertical localization was observed after bilateral aspiration lesions of A1, whereas performance at longer sound durations was unaffected. Another group of ferrets received larger lesions, encompassing both primary and nonprimary auditory cortical areas, and showed a greater deficit with performance being impaired for long- and short-duration (500- and 40-ms, respectively) stimuli. These data suggest that the integrity of the auditory cortex is required to successfully utilize spectral localization cues, which are thought to provide the basis for vertical localization, and that multiple cortical fields, including A1, contribute to this task.

Rats emit ultrasonic vocalizations (USVs) as social signals in several situations. Lesion studies have shown that rat perirhinal cortex (PR), a polymodal sensory region that is reciprocally connected with the amygdala, is critical for normal fear conditioning to so-called "22 kHz USVs". Here we evaluated single-unit responses in rat PR to 22 kHz USVs and other acoustic stimuli. One question was whether PR circuits are specifically and preferentially tuned, prior to fear conditioning, to respond to USVs and USV-like stimuli. Two 22 kHz USVs were pre-recorded from different conspecifics. Each USV consisted of a "bout" of several discrete calls. Using experimentally naïve rats, single-unit responses to the USVs were compared with responses to continuous or discontinuous tones that had the same root frequency as the USVs (19 or 22 kHz). The on/off patterns of the discontinuous tones were temporally matched to the call structure in the corresponding USVs. Compared to continuous tones, the USVs were no more likely to elicit single-unit firing changes in PR. On the other hand, the continuous tones and USVs clearly did elicit different firing patterns in many units. More specifically, the USVs sometimes elicited a transient increase in discharge frequency to each call in a bout of calls. Interestingly, the USVs and the temporally matched tone segments usually elicited similar firing patterns. The USV-elicited firing pattern in PR thus appears to be controlled by the on/off temporal structure of the calls rather than by the frequency or amplitude modulations associated with each call in a bout of calls.

Background: Mucopolysaccharidosis (MPS) IIIB (Sanfilippo Syndrome type B) is caused by a deficiency in the lysosomal enzyme N-acetyl-glucosaminidase (Naglu). Children with MPS IIIB develop disturbances of sleep, activity levels, coordination, vision, hearing, and mental functioning culminating in early death. The murine model of MPS IIIB demonstrates lysosomal distention in multiple tissues, a shortened life span, and behavioral changes. Principal findings: To more thoroughly assess MPS IIIB in mice, alterations in circadian rhythm, activity level, motor function, vision, and hearing were tested. The suprachiasmatic nucleus (SCN) developed pathologic changes and locomotor analysis showed that MPS IIIB mice start their daily activity later and have a lower proportion of activity during the night than wild-type controls. Rotarod assessment of motor function revealed a progressive inability to coordinate movement in a rocking paradigm. Purkinje cell counts were significantly reduced in the MPS IIIB animals compared to age matched controls. By electroretinography (ERG), MPS IIIB mice had a progressive decrease in the amplitude of the dark-adapted b-wave response. Corresponding pathology revealed shortening of the outer segments, thinning of the outer nuclear layer, and inclusions in the retinal pigmented epithelium. Auditory-evoked brainstem responses (ABR) demonstrated progressive hearing deficits consistent with the observed loss of hair cells in the inner ear and histologic abnormalities in the middle ear. Conclusions/significance: The mouse model of MPS IIIB has several quantifiable phenotypic alterations and is similar to the human disease. These physiologic and histologic changes provide insights into the progression of this disease and will serve as important parameters when evaluating various therapies.

The BETA2/NeuroD1 null mouse has cochlear dysplasia. Its cochlear duct is shorter than normal, there is a lack of spiral ganglion neurons, and there is hair cell disorganization. We measured vertical movements of the tectorial membrane at acoustic frequencies in excised cochleae in response to mechanical stimulation of the stapes using laser doppler vibrometry. While tuning curve sharpness was similar between wild-type, heterozygotes, and null mice in the base, null mutants had broader tuning in the apex. At both the base and the apex, null mice had less phase lag accumulation with increasing stimulus frequency than wild-type or heterozygote mice. In vivo studies demonstrated that the null mouse lacked distortion product otoacoustic emissions, and the cochlear microphonic and endocochlear potential were found to be severely reduced. Electrically evoked otoacoustic emissions could be elicited, although the amplitudes were lower than those of wild-type mice. Cochlear cross-sections revealed an incomplete partition malformation, with fenestrations within the modiolus that connected the cochlear turns. Outer hair cells from null mice demonstrated the normal pattern of prestin expression within their lateral walls and normal FM 1-43 dye entry. Overall, these data demonstrate that while tonotopicity can exist with cochlear dysplasia, traveling wave propagation is abnormally fast. Additionally, the presence of electrically evoked otoacoustic emissions suggests that outer hair cell reverse transduction is present, although the acoustic response is shaped by the alterations in cochlear mechanics.

Disinhibition of the thalamus remains the primary model of information transfer between the basal ganglia and the cortex. Yet in apparent conflict with this model, the globus pallidus, a GABAergic basal ganglia output structure, often exhibits marked increases in firing rate during movement. To investigate the translation of pallidal activity and its relay through the thalamus, we explored a basal ganglia–thalamic pathway essential for song learning in songbirds. We found that single units in the thalamic nucleus DLM of urethane-anesthetized adult male zebra finches responded selectively to playback of the bird's own song, like neurons in its upstream and downstream nuclei. Because the pallidal input to these neurons forms giant calyx-like synapses, we were able to record extracellular signals from these presynaptic terminals as well. Pallidal units were distinctly excited by song playback, suggesting an increase in GABAergic transmission in the thalamus during sensory processing. However, this overall increased firing rate was phasic, punctuated by rapid decelerations in firing rate. In several cases, we were able to record presynaptic and postsynaptic units simultaneously. Correlating the presynaptic and postsynaptic activity, we found that disinhibition of thalamus may entail pallidal firing rate decelerations rather than simple long pauses in spontaneous activity, as has long been assumed.

Transcallosal excitation and inhibition have been theorized based on the effect of callosotomy on intractable epilepsy and dichotic listening research, respectively. We studied bilateral interaction of cortical auditory neurons and found that this interaction consisted of focused facilitation and widespread lateral inhibition. The frequency modulated (FM)–FM area of the auditory cortex of the mustached bat is composed of delay-tuned neurons tuned to the combination of the emitted biosonar pulse and its echo with a specific echo delay [best delay (BD)] and consists of three subdivisions in terms of the combination sensitivity of neurons. We found that focal electric stimulation of one of these three subdivisions evoked BD shifts of delay-tuned neurons in all three subdivisions of the contralateral FM–FM area, presumably via the corpus callosum. The effect of electric stimulation of the delay-tuned neurons on the contralateral delay-tuned neurons was different depending on whether the BD of a recorded neuron was matched or unmatched in BD with that of the stimulated neurons. BD-matched neurons did not change their BDs and increased the responses at their BDs, whereas BD-unmatched neurons shifted their BDs away from the BD of the stimulated neurons and reduced their responses. The ipsilateral and contralateral BD shifts evoked by the electric stimulation were identical to each other. The contralateral modulation, in addition to the ipsilateral modulation, increases the contrast in the neural representation of the echo delay to which the stimulated neurons are tuned.

Deprivation from normal sensory input has been shown to alter tonotopic organization of the human auditory cortex. In this context, cochlear implant subjects provide an interesting model in that profound deafness is made partially reversible by the cochlear implant. In restoring afferent activity, cochlear implantation may also reverse some of the central changes related to deafness. The purpose of the present study was to address whether the auditory cortex of cochlear implant subjects is tonotopically organized. The subjects were thirteen adults with at least 3 months of cochlear implant experience. Auditory event-related potentials were recorded in response to electrical stimulation delivered at different intracochlear electrodes. Topographic analysis of the auditory N1 component (∼85 ms latency) showed that the locations on the scalp and the relative amplitudes of the positive/negative extrema differ according to the stimulated electrode, suggesting that distinct sets of neural sources are activated. Dipole modeling confirmed electrode-dependent orientations of these sources in temporal areas, which can be explained by nearby, but distinct sites of activation in the auditory cortex. Although the cortical organization in cochlear implant users is similar to the tonotopy found in normal-hearing subjects, some differences exist. Nevertheless, a correlation was found between the N1 peak amplitude indexing cortical tonotopy and the values given by the subjects for a pitch scaling task. Hence, the pattern of N1 variation likely reflects how frequencies are coded in the brain.

In this study, we investigated the relationship between c-fos expression in the auditory thalamus and corticofugal activation. The contribution of neurotransmitters and related receptors, the involvement of thalamic reticular nucleus (TRN), and the role of neuronal firing patterns in this process were also examined. The principal nuclei of the medial geniculate body (MGB) showed c-fos expression when the auditory cortex (AC) was activated by direct injection of bicuculline methobromide. However, no expression was detectable with acoustic stimuli alone. This indicated that c-fos expression in the principal nuclei of the MGB was triggered by the corticofugal projection. c-fos expression could be elicited in the MGB by direct injection of glutamate. Direct administration of acetylcholine, alternatively, had no effect. Bicuculline methobromide injection in the AC also triggered synchronized oscillatory activities sequentially in the AC and MGB. Cortically induced c-fos expression in the MGB was not mediated by a pathway involving the TRN because it remained intact after a TRN lesion with kainic acid. The present results also conclude that c-fos expression is not simply associated with firing rate, but also with neuronal firing pattern. Burst firings that are synchronized with the cortical oscillations are proposed to lead to c-fos expression in the principal nuclei of the MGB.

The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing between these areas. To determine the filter properties of rat posterior auditory field (PAF) neurons, we compared neurophysiological responses to simple tones, frequency modulated (FM) sweeps, and amplitude modulated noise and tones with responses of primary auditory cortex (A1) neurons. PAF neurons have excitatory receptive fields that are on average 65% broader than A1 neurons. The broader receptive fields of PAF neurons result in responses to narrow and broadband inputs that are stronger than A1. In contrast to A1, we found little evidence for an orderly topographic gradient in PAF based on frequency. These neurons exhibit latencies that are twice as long as A1. In response to modulated tones and noise, PAF neurons adapt to repeated stimuli at significantly slower rates. Unlike A1, neurons in PAF rarely exhibit facilitation to rapidly repeated sounds. Neurons in PAF do not exhibit strong selectivity for rate or direction of narrowband one octave FM sweeps. These results indicate that PAF, like nonprimary visual fields, processes sensory information on larger spectral and longer temporal scales than primary cortex.

Cochlear fibrocytes play important roles in normal hearing as well as in several types of sensorineural hearing loss attributable to inner ear homeostasis disorders. Recently, we developed a novel rat model of acute sensorineural hearing loss attributable to fibrocyte dysfunction induced by a mitochondrial toxin. In this model, we demonstrate active regeneration of the cochlear fibrocytes after severe focal apoptosis without any changes in the organ of Corti. To rescue the residual hearing loss, we transplanted mesenchymal stem cells into the lateral semicircular canal; a number of these stem cells were then detected in the injured area in the lateral wall. Rats with transplanted mesenchymal stem cells in the lateral wall demonstrated a significantly higher hearing recovery ratio than controls. The mesenchymal stem cells in the lateral wall also showed connexin 26 and connexin 30 immunostaining reminiscent of gap junctions between neighboring cells. These results indicate that reorganization of the cochlear fibrocytes leads to hearing recovery after acute sensorineural hearing loss in this model and suggest that mesenchymal stem cell transplantation into the inner ear may be a promising therapy for patients with sensorineural hearing loss attributable to degeneration of cochlear fibrocytes.

Plasticity studies suggest that behavioral relevance can change the cortical processing of trained or conditioned sensory stimuli. However, whether this occurs in the context of natural communication, where stimulus significance is acquired through social interaction, has not been well investigated, perhaps because neural responses to species-specific vocalizations can be difficult to interpret within a systematic framework. The ultrasonic communication system between isolated mouse pups and adult females that either do or do not recognize the calls' significance provides an opportunity to explore this issue. We applied an information-based analysis to multi- and single unit data collected from anesthetized mothers and pup-naïve females to quantify how the communicative significance of pup calls affects their encoding in the auditory cortex. The timing and magnitude of information that cortical responses convey (at a 2-ms resolution) for pup call detection and discrimination was significantly improved in mothers compared to naïve females, most likely because of changes in call frequency encoding. This was not the case for a non-natural sound ensemble outside the mouse vocalization repertoire. The results demonstrate that a sensory cortical change in the timing code for communication sounds is correlated with the vocalizations' behavioral relevance, potentially enhancing functional processing by improving its signal to noise ratio.

Purpose The purposes were (a) to compare masking of consonant bursts by adjacent vowels for listeners with and without hearing loss and (b) to determine the extent to which the temporal intraspeech masking can be reduced by a simulated hearing-aid frequency-response shaping. Method Fourteen adults with sensorineural hearing loss and 10 with normal hearing participated. Seven of the participants with hearing loss had flat or gradually sloping audiograms, and 7 had steeply sloping losses. Stimuli consisted of 3 consonant bursts (/t/, /p/, /k/) presented in isolation and in vowel-consonant-vowel combinations using the vowel /a/ with formant transition information removed. Normal-hearing listeners were tested using unfiltered stimuli. Listeners with hearing loss were tested using unfiltered stimuli and stimuli filtered to approximate a hearing aid frequency response prescribed by NAL-R. All listeners were tested under earphones at the most comfortable level for the vowel stimulus. Temporal intraspeech masking was quantified as the threshold shift produced by the adjacent vowels. Results Average intraspeech masking for listeners with steeply sloping hearing loss was significantly higher than that of normal-hearing listeners and those with flat/gradually sloping losses. Greater intraspeech masking was observed for /t/ and /p/ than for /k/. On average, frequency shaping significantly reduced the amount of intraspeech masking for listeners with steeply sloping hearing losses. Even with appropriate amplification/spectral shaping, however, temporal intraspeech masking remained greater than normal for several individuals. Conclusion Findings suggest that some individuals with steeply sloping losses may need additional signal processing to supplement frequency shaping to overcome the effect of temporal intraspeech masking.

Auditory-evoked potentials (AEPs) have become a widely utilized measure of hearing sensitivity. Most investigators use pharmacological paralysis to reduce myogenic noise and immobilize the animal for stable electrical recordings, but additional anesthesia is generally not used because the most commonly available fish anesthetic, the cholinergic antagonist tricaine methanosulfate (MS222), is known to disrupt hair cell and primary afferent physiology. Anesthetic agents that do not interfere with auditory function would be a useful adjunct to paralytic immobilization and would reduce any possible distress incurred by prolonged immobilization. In this report we tested the opiate anesthetic fentanyl and compared hearing thresholds in immobilized versus immobilized and anesthetized animals. Short-term effects of mild MS222 anesthesia were also measured via evoked potential audiometry. Animals were tested before and after fentanyl injection (100, 500 and 2500 microg g(-1) fish body-weight) using standard evoked potential audiometry. Tone pips, 0.2-3 kHz, from an aerial loudspeaker served as stimuli. Fentanyl altered evoked potential waveforms slightly but did not alter estimated threshold sensitivity. These results suggest fentanyl be considered as a possible addition to AEP techniques in goldfish (Carassius auratus) and poikilothermic vertebrates generally.

Individuals with age-related hearing loss often have difficulty understanding complex sounds such as basic speech. The C57BL/6 mouse suffers from progressive sensorineural hearing loss and thus is an effective tool for dissecting the neural mechanisms underlying changes in complex sound processing observed in humans. Neural mechanisms important for processing complex sounds include multiple tuning and combination sensitivity, and these responses are common in the inferior colliculus (IC) of normal hearing mice. We examined neural responses in the IC of C57Bl/6 mice to single and combinations of tones to examine the extent of spectral integration in the IC after age-related high frequency hearing loss. Ten percent of the neurons were tuned to multiple frequency bands and an additional 10% displayed non-linear facilitation to the combination of two different tones (combination sensitivity). No combination-sensitive inhibition was observed. By comparing these findings to spectral integration properties in the IC of normal hearing CBA/CaJ mice, we suggest that high frequency hearing loss affects some of the neural mechanisms in the IC that underlie the processing of complex sounds. The loss of spectral integration properties in the IC during aging likely impairs the central auditory system's ability to process complex sounds such as speech.

When listening to two tones at frequency f1 and f2 (f2>f1), one can hear pitches not only at f1 and f2 but also at distortion frequencies f2-f1, (n+1)f1-nf2, and (n+1)f2-nf1 (n=1,2,3...). Such two-tone distortion products (DPs) also can be measured in the ear canal using a sensitive microphone. These ear-generated sounds are called otoacoustic emissions (OAEs). In spite of the common applications of OAEs, the mechanisms by which these emissions travel out of the cochlea remain unclear. In a recent study, the basilar membrane (BM) vibration at 2f1-f2 was measured as a function of the longitudinal location, using a scanning laser interferometer. The data indicated a forward traveling wave and no measurable backward wave. However, this study had a relatively high noise floor and high stimulus intensity. In the current study, the noise floor of the BM measurement was significantly decreased by using reflective beads on the BM, and the vibration was measured at relatively low intensities at more than one longitudinal location. The results show that the DP phase at a basal location leads the phase at an apical location. The data indicate that the emission travels along the BM from base to apex as a forward traveling wave, and no backward traveling wave was detected under the current experimental conditions.

When measured behaviorally, older adults with normal hearing have poorer intensity discrimination thresholds than younger adults, but only at lower frequencies. Poor intensity discrimination at lower but not higher frequencies for older adults can be associated with an age-related decline in temporal processing. The current study was designed to assess age-related effects on intensity discrimination at 500 and 3000 Hz using the cortical auditory evoked potential, N1--P2. Subjects were 10 younger and 10 older adults with normal hearing. The N1--P2 was elicited by an intensity increase in an otherwise continuous pure tone presented at 70 dB SPL. Intensity increments ranged from 0 dB to 5 dB at 500 Hz and from 0 d B to 8 d B at 3000 Hz in 1-dB steps. Intensity discrimination threshold was defined as the smallest intensity change needed to evoke an N1-P2 response. Consistent with behavioral measures, N1-P2 response thresholds were significantly higher for older subjects than younger subjects at 500 Hz but did not differ significantly at 3000 Hz. In addition, N1 and P2 latencies for older subjects were significantly prolonged at 500 Hz, but not at 3000 Hz. As intensity increments increased above threshold, amplitudes tended to be larger in older than in younger subjects, however, these differences were not statistically significant. In older subjects, response latencies and amplitudes were significantly larger at 500 Hz than at 3000 Hz. In younger subjects, response latencies and amplitudes were similar across frequency. Similar intensity discrimination thresholds and age-related differences for behavioral measures and evoked potentials support the notion that the N1-P2 measures reflect the physiological detection of intensity change which in turn relates to intensity discrimination. A possible explanation for the decreased intensity discrimination at low frequencies, and enhanced amplitudes with prolonged latencies in older subjects is an age-related decline in inhibitory control within the central auditory nervous system.

The primary auditory cortex is characterized by a tonotopic map and a clustered organization of binaural properties. The factors involved in the development of overlain representation of these two properties are unclear. We addressed this issue in the auditory cortex of the pallid bat. The adult pallid bat cortex contains a systematic relationship between best frequency (BF) and binaural properties. Most neurons with BF<30 kHz are binaurally inhibited (EO/I), while most neurons with BF>30 kHz are monaural (EO). As in other species, binaural properties are clustered. The EO/I cluster contains a systematic map of interaural intensity difference (IID) sensitivity. We asked if these properties are present at the time the bat acquires its full audible range (postnatal day [P] 15). Tonotopy, relationship between BF and binaural properties, and the map of IID sensitivity are adult-like at P15. However, binaural facilitation is only observed in pups older than P25. Frequency selectivity shows a BF-dependent sharpening during development. Thus, overlain representation of binaural properties and tonotopy in the pallid bat cortex is remarkably adult-like at an age when the full audible range is first present, suggesting an experience-independent development of overlapping feature maps.

Dorsal root injury (DRI) disrupts the flow of sensory information to the spinal cord. Although primary afferents do not regenerate to their original targets, spontaneous recovery can, by unknown mechanisms, occur after DRI. Here, we show that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not nerve growth factor or neurotrophin-4, are upregulated in the spinal gray matter after DRI. Because endognous BDNF and NT-3 have well established roles in synaptic and axonal plasticity, we hypothesized that they contributed to spontaneous recovery after DRI. We first developed a model of DRI-induced mechanosensory dysfunction: rat C7/8 DRI produced a deficit in low-threshold cutaneous mechanosensation that spontaneously improved within 10 d but did not recover completely. To determine the effects of endogenous BDNF and NT-3, we administered TrkB-Fc or TrkC-Fc fusion proteins throughout the recovery period. To our surprise, TrkB-Fc stimulated complete recovery of mechanosensation by 6 d after DRI. It also stimulated mechanosensory axon sprouting but prevented deafferentation-induced serotonergic sprouting. TrkC-Fc had no effect on low-threshold mechanosensory behavior or axonal plasticity. There was no mechanosensory improvement with single-bolus TrkB-Fc infusions at 10 d after DRI (despite significantly reducing rhizotomy-induced cold pain), indicating that neuromodulatory effects of BDNF did not underlie mechanosensory recovery. Continuous infusion of the pan-neurotrophin antagonist K252a also stimulated behavioral and anatomical plasticity, indicating that these effects of TrkB-Fc treatment occurred independent of signaling by other neurotrophins. These results illustrate a novel, plasticity-suppressing effect of endogenous TrkB ligands on mechanosensation and mechanosensory primary afferent axons after spinal deafferentation.