Reliability and Precision of the Mouse Calyx of Held Synapse

Abstract

Traditionally, the calyx of Held synapse is viewed as a highly reliable relay in the sound localization circuit of the auditory brainstem, with every presynaptic action potential triggering a postsynaptic action potential in vivo. However, this view is at odds with slice recordings that report large short-term depression (STD). To investigate the reliability and precision of this synapse, we compared slice and in vivo recordings from medial nucleus of the trapezoid body neurons of young adult mice. We show that the extracellularly recorded complex waveform can be used to estimate both presynaptic release and postsynaptic excitability. Whereas under standard slice conditions the synapse underwent large STD, both extracellular and whole-cell recordings indicated that in vivo the size of the EPSPs was independent of recent history. The estimated quantal content was typically Ͻ20 in vivo, much lower than in the resting synapse under standard slice conditions. However, due to the large quantal size and summation of EPSPs, the safety factor of this synapse was generally still sufficiently large and postsynaptic failures were observed only infrequently in vivo. When present, failures were typically due to stochastic fluctuations in EPSP size or postsynaptic spike depression. In vivo, the calyx of Held synapse thus functions as a tonic synapse. The price it pays for its low release probability is an increase in jitter and synaptic latency and occasional postsynaptic failures.

Factors Controlling the Input–Output Relationship of Spherical Bushy Cells in the Gerbil Cochlear Nucleus

“…We used the first derivative of the simulated whole-cell potential as an approximation of our juxtacellular in vivo recordings (Lorteije et al, 2009). In fact, the time derivative resembled the waveforms seen in juxtacellular recordings from SBCs in the intact AVCN in many aspects (with the exception of a prespike).…”

“…In fact, the time derivative resembled the waveforms seen in juxtacellular recordings from SBCs in the intact AVCN in many aspects (with the exception of a prespike). For a more in-depth model of the juxtacellular recording situation, compare the work of Lorteije et al (2009). Consistent with the analysis of our in vivo data, we used the maximum slope of the simulated eEPSP component to estimate the strength of the synaptic event, which corresponds to the maximum of the second derivative of the simulated whole-cell potential (iEPSPЉ).…”

“…Recovery models of spike depression and synaptic facilitation were fitted to data from spontaneous recordings (Varela et al, 1997;Lorteije et al, 2009). Briefly, a time-dependent state variable was calculated, which was cumulatively decreased (depression) or increased (facilitation) by a given amount whenever a spike or event occurred.…”

“…The complex waveform consists of a prespike, which presumably reflects the AP of a nearby endbulb of Held, and an extracellularly recorded EPSP, which may or may not trigger an AP (Pfeiffer, 1966;Typlt et al, 2010). Lorteije et al (2009) showed that similar waveforms recorded from the calyx of Held synapse can be used to estimate both the strength of synaptic transmission and postsynaptic excitability. Here, we analyze juxtacellular recordings from SBCs in the rostral AVCN of anesthetized adult gerbils and show that the complex waveforms can also be used to quantify synaptic inhibition, allowing identification of the different factors governing precision and reliability of the SBC in vivo.…”

Calretinin Regulates Ca2+-dependent Inactivation and Facilitation of Cav2.1 Ca2+ Channels through a Direct Interaction with the α12.1 Subunit

“…Electrophysiological recordings at the Calyx of Held synapse, usually done in brainstem slices from juvenile rats (postnatal day 8 -10), indicate that the presynaptic Ca v 2.1 channels undergo CDI and CDF (8 -10, 54). Given our findings that CR inhibits CDI and enhances CDF, the developmental increase in CR would be expected to promote the activity-dependent Ca 2ϩ influx that may limit synaptic depression and/or increase reliability in the mature Calyx of Held synapse (55). As our coimmunoprecipitation of Ca v 2.1 with CR from mouse cerebellum would indicate, CR-Ca v 2.1 complexes may play a role in cerebellar granule cells, the predominant cell types expressing CR in the cerebellum (56,57).…”