Noise — random disturbances of signals — poses a fundamental problem for information processing and affects all aspects of nervous-system function. However, the nature, amount and impact of noise in the nervous system have only recently been addressed in a quantitative manner. Experimental and computational methods have shown that multiple noise sources contribute to cellular and behavioural trial-to-trial variability. We review the sources of noise in the nervous system, from the molecular to the behavioural level, and show how noise contributes to trial-to-trial variability. We highlight how noise affects neuronal networks and the principles the nervous system applies to counter detrimental effects of noise, and briefly discuss noise's potential benefits.

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Noise in the nervous system.

Alternative splicing: increasing diversity in the proteomic world.

The Presynaptic Active Zone

Congenital Deafness and Sinoatrial Node Dysfunction in Mice Lacking Class D L-Type Ca2+ Channels

Joris, P. X., C. E. Schreiner, and A. Rees. Neural Processing of Amplitude-Modulated Sounds. Physiol Rev 84: 541–577, 2004; 10.1152/physrev.00029.2003.—Amplitude modulation (AM) is a temporal featu...

https://www.physiology.org/doi/pdf/10.1152/physrev.00029.2003

Neural processing of amplitude-modulated sounds.

Neurotransmitters are released continuously at ribbon synapses in the retina and cochlea. Notably, a single ribbon synapse of inner hair cells provides the entire input to each cochlear afferent fiber. We investigated hair cell transmitter release in the postnatal rat cochlea by recording excitatory postsynaptic currents (EPSCs) from afferent boutons directly abutting the ribbon synapse. EPSCs were carried by rapidly gating AMPA receptors. EPSCs were clustered in time, indicating the possibility of coordinate release. Amplitude distributions of spontaneous EPSCs were highly skewed, peaking at 0.4 nS and ranging up to 20 times larger. Hair cell depolarization increased EPSC frequency up to 150 Hz without altering the amplitude distribution. We propose that the ribbon synapse operates by multivesicular release, possibly to achieve high-frequency transmission.

http://clm.utexas.edu/systemsjc/wp-content/uploads/2011/09/Glowatzki-and-Fuchs-Nature-Neurosci.pdf

Transmitter release at the hair cell ribbon synapse.

▪ Abstract Mechanosensory hair cells of the vertebrate inner ear contribute to acoustic tuning through feedback processes involving voltage-gated channels in the basolateral membrane and mechanotransduction channels in the apical hair bundle. The specific number and kinetics of calcium-activated (BK) potassium channels determine the resonant frequency of electrically tuned hair cells. Kinetic variation among BK channels may arise through alternative splicing of slo gene mRNA and combination with modulatory β subunits. The number of transduction channels and their rate of adaptation rise with hair cell response frequency along the cochlea's tonotopic axis. Calcium-dependent feedback onto transduction channels may underlie active hair bundle mechanics. The relative contributions of electrical and mechanical feedback to active tuning of hair cells may vary as a function of sound frequency.

Mechanisms of hair cell tuning.

Efferent feedback onto sensory organs provides a means to modulate input to the central nervous system. In the developing mammalian cochlea, inner hair cells are transiently innervated by efferent fibers, even before sensory function begins. Here, we show that neonatal inner hair cells are inhibited by cholinergic synaptic input before the onset of hearing. The synaptic currents, as well as the inner hair cell9s response to acetylcholine, are mediated by a nicotinic (α9-containing) receptor and result in the activation of small-conductance calcium-dependent potassium channels.

http://science.sciencemag.org/content/sci/288/5475/2366.full.pdf

Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea.

Sensory synapses of the visual and auditory systems must faithfully encode a wide dynamic range of graded signals, and must be capable of sustained transmitter release over long periods of time. Functionally and morphologically, these sensory synapses are unique: their active zones are specialized in several ways for sustained, rapid vesicle exocytosis, but their most striking feature is an organelle called the synaptic ribbon, which is a proteinaceous structure that extends into the cytoplasm at the active zone and tethers a large pool of releasable vesicles. But precisely how does the ribbon function to support tonic release at these synapses? Recent genetic and biophysical advances have begun to open the 'black box' of the synaptic ribbon with some surprising findings and promise to resolve its function in vision and hearing.

The diverse roles of ribbon synapses in sensory neurotransmission

Cochlear hair cells are thought to be inhibited by the release of ACh from efferent neurons. Several studies have implicated Ca2+ as a postsynaptic intermediary in hair cell inhibition, but its role remains unproven. We have made whole-cell, tight-seal recordings from single short hair cells (the avian analog of outer hair cells in the mammalian cochlea), isolated from the chick's cochlea, to determine the mechanism of cholinergic inhibition. These cells hyperpolarized upon exposure to ACh, although a brief depolarization preceded the much larger, longer- lasting hyperpolarization. In voltage clamp ACh evoked an outward current that reversed in sign near the K+ equilibrium potential. A small, transient inward current preceded the predominant outward current. The ACh-evoked K+ current depended on Ca2+ in the external saline, or could be prevented when the cell was dialyzed with the rapid Ca2+ buffer BAPTA. In BAPTA-loaded cells a residual inward current was seen. This activated with very little delay upon exposure of the cell to ACh and reversed near 0 mV membrane potential. Thus, the hair cell ACh receptor appears to be a nonspecific cation channel through which Ca2+ enters and triggers the opening of nearby Ca(2+)-activated K+ channels. However, the ACh-evoked K+ channels are not the same as the “maxi” K+ channels activated by Ca2+ influx through voltage-gated Ca2+ channels in these same cells.

https://www.jneurosci.org/content/jneuro/12/3/800.full.pdf

Paul A. Fuchs

Papers

Transmitter release at the hair cell ribbon synapse.

Mechanisms of hair cell tuning.

Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea.

The diverse roles of ribbon synapses in sensory neurotransmission

Cholinergic inhibition of short (outer) hair cells of the chick's cochlea