Efferent Input to Inner Hair Cells Reappears during Age-Related Hearing Loss
Stephen Paul Zachary and Paul Albert Fuchs
(see pages 9701–9706)
Before the onset of hearing in rodent pups, efferent cholinergic axons transiently innervate cochlear inner hair cells (IHCs). During the first 2 postnatal weeks, activation of nicotinic acetylcholine receptors (nAChRs) on IHCs inhibits the cells, and this is thought to help shape developing auditory circuits. Although efferent innervation of IHCs subsequently disappears, electron micrographic studies have noted the presence of presynaptic terminals abutting IHCs in old C57 mice—a strain that exhibits age-dependent hearing loss. Whether these contacts represent functional synapses, and if so, how the synapses affect IHCs, has been unclear. Zachary and Fuchs now answer these questions.
Whole-cell recordings from excised portions of the apical cochlear epithelium indicated that postsynaptic currents were present in IHCs from 1-week-old, but not 1-month-old C57 mice. Postsynaptic currents were again detected in IHCs after 9 months, and the proportion of IHCs exhibiting such currents increased to ∼50% by 12 months. The reappearance of postsynaptic currents in IHCs coincided with increases in auditory thresholds, loss of ribbon synapses between IHCs and spiral ganglion dendrites, and loss of outer hair cells.
Like the postsynaptic currents measured in IHCs of newborn mice, those in aged IHCs were induced by acetylcholine and required nAChRs containing the α9 subunit. Furthermore, the currents were inhibitory and mediated by small-conductance calcium-activated potassium channels. These data indicate that cholinergic efferent inhibition similar to that present in immature IHCs re-emerges during age-dependent hearing loss in C57 mice.
It should be noted that C57 mice harbor a genetic mutation that alters a component of the tip links required for sound transduction by hair cells. Therefore, future experiments should determine whether efferent inhibition re-emerges in age-related hearing loss occurring in the absence of genetic predisposition. In addition, whether the re-emergence of efferent inhibition exacerbates hearing loss or attenuates it—for example by minimizing excitotoxic damage—is an important question for future research.
V1 Activity Reflects Reward Rate and Timing
Camila L. Zold and Marshall G. Hussain Shuler
(see pages 9603–9614)
Experience-dependent plasticity of the visual system has been a rich vein of research for decades. Much work has focused on the effects of visual experience during development, particularly how this plasticity shapes feature-detection circuits in primary visual cortex (V1). But visual experience also alters V1 responses in adults. For example, repeated presentation of the same stimulus increases the amplitude of stimulus-evoked potentials recorded in V1. Recent studies have also found that rodent V1 plasticity involves more than simply enhancing representation of the physical attributes of visual stimuli (reviewed in Gavornik and Bear, 2014, Learn Mem 21:527). For example, after a visual stimulus has repeatedly been paired with a reward, V1 activity persists after the visual stimulus disappears and continues until the time reward is expected. Furthermore, if a given sequence of visual stimuli is presented repeatedly and one of the stimuli is then omitted, V1 responds as if that stimulus were still presented.
Light cues associated with reward sometimes elicit oscillations in V1 that persist from the time of cue presentation (shaded area) until the median reward delivery time (dashed vertical line). See Zold and Hussain Shuler for details.
Zold and Hussain Shuler provide evidence that rodent V1 also encodes information about the recent history of reward associated with visual stimuli. They found that after light cues were repeatedly paired with delayed rewards delivered on 50% of trials, the cues began to evoke 6–9 Hz oscillations on some trials. Like in previous studies, the timing of oscillations—if they occurred—changed over the course of training. Initially, the duration reflected the intensity of the light stimulus, but this relationship was gradually lost and the duration instead began to reflect the expected time of reward. The probability of evoking an oscillation also varied over the course of training. Initially, the probability was determined primarily by the intensity of the light cue. But after the task and the reward timing were learned, the probability of evoking an oscillation was additionally influenced by the recent reward rate.
These results clearly indicate that V1 does not simply encode the physical attributes of a stimulus. What information visually evoked oscillations encode remains unknown, but Zold and Hussain Shuler suggest they reflect the behavioral relevance of visual cues. Thus, oscillations are evoked more often as the rat learns that the cues signal reward and less often as the rat becomes sated.
