Katz, E. | bioRxiv Science

bioRxiv2018

Developmental synaptic changes at the transient olivocochlear-inner hair cell synapse

In the mature mammalian cochlea, inner hair cells (IHCs) are mainly innervated by afferent fibers that convey sound information to the central nervous system. During postnatal development, however, medial olivocochlear (MOC) efferent fibers transiently innervate the IHCs. The MOC-IHC synapse, functional from postnatal day (P)0 to hearing onset (P12), undergoes dramatic changes in the sensitivity to acetylcholine (ACh) and in the expression of key postsynaptic proteins. To evaluate whether there are associated changes in the properties of ACh release during this period, we used a cochlear preparation from mice at P4, P6-7 and P9-11 and monitored transmitter release from MOC terminals in voltage-clamped IHCs in the whole-cell configuration. The quantum content increased 5.6x from P4 to P9-11 due to increases in the size and replenishment rate of the readily releasable pool (RRP) of synaptic vesicles, without changes in their probability of release (Pvesicle) or quantum size. This strengthening in transmission was accompanied by changes in the short-term plasticity (STP) properties, which switched from facilitation at P4 to depression at P9-11. We have previously shown that at P9-11, ACh release is supported by P/Q and N-type voltage-gated calcium channels (VGCCs) and negatively regulated by BK potassium channels activated by Ca2+ influx through L-type VGCCs. We now show that at P4 and P6-7, release is mediated by P/Q-, R- and L-type VGCCs. Interestingly, L-type VGCCs have a dual role: they both support release and fuel BK channels, suggesting that at immature stages the presynaptic proteins involved in release are less compartmentalized.\n\nSignificance statementDuring postnatal development prior to the onset of hearing, cochlear IHCs present spontaneous Ca2+ action potentials which release glutamate at the first auditory synapse in the absence of sound stimulation. The IHC Ca2+ action potential frequency pattern, which is crucial for the correct establishment and function of the auditory system, is regulated by the efferent MOC system that transiently innervates IHCs during this period. We show short-term synaptic plasticity properties of the MOC-IHC synapse that tightly shape this critical developmental period.

neuroscience↗

bioRxiv2017

Sub-threshold resonance organizes activity and optimizes learning in neural networks.

Network oscillations across and within brain areas are critical for learning and performance in memory tasks. While a large amount of work has focused on the generation of neural oscillations, their effects on neuronal populations spiking activity and information encoding is less known. Here, we use computational modeling and in vivo recording to demonstrate that a shift in sub-threshold resonance can interact with oscillating input to ensure that networks of neurons properly encode new information represented in external inputs to the weights of recurrent synaptic connections. Using a neuronal network model, we find that due to an input-current dependent shift in their resonance response, individual neurons in a network will arrange their phases of firing to represent varying strengths of their respective inputs. As networks encode information, neurons fire more synchronously, and this effect limits the extent to which further \"learning\" (in the form of changes in synaptic strength) can occur. We also demonstrate that sequential patterns of neuronal firing can be accurately stored in the network; these sequences are later reproduced without external input (in the context of sub-threshold oscillations) in both the forward and reverse directions (as has been observed following learning in vivo). To test whether a similar mechanism could act in vivo, we show that periodic stimulation of hippocampal neurons coordinates network activity and functional connectivity in a frequency-dependent manner. We conclude that sub-threshold resonance provides a plausible network-level mechanism to accurately encode and retrieve information without over-strengthening connections between neurons.

neuroscience↗