The dynamics of synaptic transmission between neurons plays a major role in neural information processing (Abbott and Regehr, 2004
). While transmission is fundamentally probabilistic, the release of neurotransmitters is also highly dependent on the recent history of activity at a particular synapse, and both the release probability and the temporal dynamics of release can be modulated. Changes in the strength of synapses can be divided into those transient effects that last for seconds to minutes, or short-term plasticity, and those that last for tens of minutes to days (or even years), or long-term plasticity. In this review, we will focus on the role of short-term plasticity, and on the changes in release and short-term plasticity that follow hearing loss, at the first synapses in the central auditory pathway.
Short-term plasticity can appear as either depression or facilitation of synaptic strength, and a single synapse can exhibit either or both of these phenomena at any given time. In general, depressing synapses have a high release probability at rest, while facilitating synapses have a low release probability. The depression and facilitation between sequential presynaptic action potentials can be viewed as a combination of the time-dependent changes in the availability of releasable vesicles, in vesicular release probability and of postsynaptic receptor sensitivity to the released transmitter (i.e., desensitization). In depressing synapses, repeated presynaptic activation of a synapse over a time frame of tens of millseconds to seconds results in reduced transmitter release and/or a reduced postsynaptic response over time. For constant-rate stimulation (i.e., regular trains), depression is generally rate-dependent (model calculations of the strength of the synaptic response are shown for different rates in ), so that greater depression is seen at high stimulus rates (corresponding to shorter interstimulus intervals). Consequently, depressing synapses tend to decrease the strength of synaptic transmission after the onset of a burst of action potentials at a high rate. From the standpoint of the postsynaptic cell, this means that high-rate information is suppressed, relative to low-frequency events. Depressing synapses can be viewed as low-pass filters of presynaptic spike trains, and thus can contribute to the adaptation of neural responses to sustained sensory input. On the other hand, some synapses show facilitation for certain rates of presynaptic activity. In this case, as the presynaptic rate increases (up to a point), the release probability increases. Such synapses can enhance responses to higher-frequency presynaptic activity, and thus act as high-pass filters (Grande and Spain, 2005
). From an information theoretic standpoint, these differences in synaptic dynamics convey (or emphasize) specific aspects of the information contained in the timing of presynaptic action potentials to the postsynaptic neuron (Cook et al., 2003
; Fuhrmann et al., 2002
Figure 1 Schematic of synaptic depression at normal auditory synapses as modeled from measurements in mouse cochlear nucleus. Each plot shows the normalized EPSC amplitude during stimulation with regular trains at different frequencies from 20 to 400 Hz, with (more ...)
What determines the release probability of a synapse, and in turn, whether it facilitates or depresses during changes in the firing rate of the parent axon? Synapses from a single presynaptic cell that innervate different types of target cells can have very distinct release probabilities (Mancilla and Manis, 2009
; Markram et al., 1998
), and the release probabilities from synapses of one class of afferent cell that innervate a specific population of target cells often are more similar than those innervating different targets (Dittman et al., 2000
). This relationship seems to hold across both excitatory and inhibitory synapses, and across multiple regions of the brain. Recent studies in the avian and mammalian cochlear nucleus also suggest that auditory nerve endings on different sets of target cells may show different release dynamics (Cao and Oertel, 2010
; MacLeod et al., 2007
). In particular, endings on bushy cells depress more rapidly than endings on non-bushy cells (T-stellate cells or regular-spiking neurons of the avian nucleus angularis). This is summarized in , which shows a comparison between the rates and magnitudes of depression in a model based on measurements made in bushy and T-stellate cells of the mouse ventral cochlear nucleus (VCN).
The presence of ongoing spontaneous or background discharge may also chronically bias release mechanisms (Hermann et al., 2007
; Wang et al., 2010
). Even relatively low afferent rates, such as 10–20 Hz, which is well within the rate of the spontaneous activity rates of auditory nerve fibers (in mouse Taberner and Liberman, 2005
), can lead to a modest depression of release (Wang et al., 2010
). It is also likely that the longer-term history of activity in an afferent may engage slowly varying homeostatic mechanisms that regulate how transmitter is released. In the context of the auditory system, sensory deprivation or hearing loss might be expected to influence the transfer of information, as might the introduction of artificial stimulus patterns by cochlear implants. Such changes in presynaptic function are presaged by demonstrations of the plasticity of endbulb morphology in cats and mice with congenital hearing loss (Lee et al., 2003
; Ryugo et al., 1997
). As discussed below, hearing loss can alter synaptic efficacy and synaptic dynamics at auditory nerve synapses, although the details and overall consequences appear to depend on the etiology of the loss.
In this review, we will focus on short-term plasticity of auditory nerve synapses in the cochlear nucleus, and their potential modulation by hearing loss. Most of the review will focus on the endbulb synapse in the VCN in rodents, although we will also touch upon endbulbs from other model systems and other synapses in the cochlear nucleus whose release parameters might be affected by hearing loss.