Explore the vast range of titles available.

A centre for neural control The axon initial segment (AIS) at the base of each nerve fibre, where clusters of sodium channels generate the action potential that then propagates along the axon, is a focus of much attention from neuroscientists working on the nature of neuronal excitability. As the source of a nerve impulse, it seems a logical point at which to regulate neural activity. Two papers in this issue confirm that the AIS is a source of intrinsic neuronal plasticity. Matthew Grubb and Juan Burrone show that electrical activity reversibly alters the position of the AIS in cultured hippocampal neurons. They suggest that the resulting increase in intrinsic excitability may fine-tune neuronal excitability during development, and point to potential targets for the control of epilepsy. Hiroshi Kuba, Yuki Oichi and Harunori Ohmori show that the size of the AIS increases in bird auditory neurons deprived of sound stimulation. Again intrinsic excitability increases, possibly contributing to the maintenance of the auditory pathway. Such neuronal plasticity may compensate some forms of hearing loss. A nerve cell sends signals to others through action potentials, which begin at the 'initial segment' of the neuron's axon. Here it is shown that the length of this initial segment increases in bird auditory neurons that have been deprived of auditory stimulation. The resulting increase in intrinsic excitability — the tendency to fire action potentials — represents a new form of neuronal plasticity and might contribute to the maintenance of the auditory pathway after hearing loss. Deprivation of afferent inputs in neural circuits leads to diverse plastic changes in both pre- and postsynaptic elements that restore neural activity 1 . The axon initial segment (AIS) is the site at which neural signals arise 2 , 3 , and should be the most efficient site to regulate neural activity. However, none of the plasticity currently known involves the AIS. We report here that deprivation of auditory input in an avian brainstem auditory neuron leads to an increase in AIS length, thus augmenting the excitability of the neuron. The length of the AIS, defined by the distribution of voltage-gated Na + channels and the AIS anchoring protein, increased by 1.7 times in seven days after auditory input deprivation. This was accompanied by an increase in the whole-cell Na + current, membrane excitability and spontaneous firing. Our work demonstrates homeostatic regulation of the AIS, which may contribute to the maintenance of the auditory pathway after hearing loss. Furthermore, plasticity at the spike initiation site suggests a powerful pathway for refining neuronal computation in the face of strong sensory deprivation.

Olfactory receptor neurons (ORNs) use odour-induced intracellular cAMP surge to gate cyclic nucleotide-gated nonselective cation (CNG) channels in cilia. Prolonged exposure to cAMP causes calmodulin-dependent feedback-adaptation of CNG channels and attenuates neural responses. On the other hand, the odour-source searching behaviour requires ORNs to be sensitive to odours when approaching targets. How ORNs accommodate these conflicting aspects of cAMP responses remains unknown. Here, we discover that olfactory marker protein (OMP) is a major cAMP buffer that maintains the sensitivity of ORNs. Upon the application of sensory stimuli, OMP directly captured and swiftly reduced freely available cAMP, which transiently uncoupled downstream CNG channel activity and prevented persistent depolarization. Under repetitive stimulation, OMP -/- ORNs were immediately silenced after burst firing due to sustained depolarization and inactivated firing machinery. Consequently, OMP -/- mice showed serious impairment in odour-source searching tasks. Therefore, cAMP buffering by OMP maintains the resilient firing of ORNs. The physiological role of the olfactory marker protein (OMP) has been elusive. Here, the authors demonstrate that OMP buffers cAMP and modulates cAMP-gated channel activity upon sensory stimulation, maintaining neuronal firing during odour-source searching.

Tuning the nerves Different neurons initiate their action potentials (or spikes) at different points down their axons, but the functional implications of this have been unclear. Kuba et al . focus on nerve cells in a bird's auditory system: the nucleus laminaris is a binaural coincidence detector, and is a good model for examining this phenomenon. They find that neurons that initiate spikes closer to the cell body (or soma) are tuned to sounds with lower frequencies. Computer modelling suggests that spike initiation sites may be key to coincidence detection by other neurons as well. Study of nerve cells in a bird's auditory system shows that those where spikes initiate closer to the cell body (or soma) are tuned to sounds with lower frequencies. Computer modelling suggests that spike initiation sites may also be key to coincidence detection by other neurons. Neurons initiate spikes in the axon initial segment or at the first node in the axon 1 , 2 , 3 , 4 . However, it is not yet understood how the site of spike initiation affects neuronal activity and function. In nucleus laminaris of birds, neurons behave as coincidence detectors for sound source localization and encode interaural time differences (ITDs) separately at each characteristic frequency (CF) 5 , 6 , 7 . Here we show, in nucleus laminaris of the chick, that the site of spike initiation in the axon is arranged at a distance from the soma, so as to achieve the highest ITD sensitivity at each CF. Na + channels were not found in the soma of high-CF (2.5–3.3 kHz) and middle-CF (1.0–2.5 kHz) neurons but were clustered within a short segment of the axon separated by 20–50 μm from the soma; in low-CF (0.4–1.0 kHz) neurons they were clustered in a longer stretch of the axon closer to the soma. Thus, neurons initiate spikes at a more remote site as the CF of neurons increases. Consequently, the somatic amplitudes of both orthodromic and antidromic spikes were small in high-CF and middle-CF neurons and were large in low-CF neurons. Computer simulation showed that the geometry of the initiation site was optimized to reduce the threshold of spike generation and to increase the ITD sensitivity at each CF. Especially in high-CF neurons, a distant localization of the spike initiation site improved the ITD sensitivity because of electrical isolation of the initiation site from the soma and dendrites, and because of reduction of Na + -channel inactivation by attenuating the temporal summation of synaptic potentials through the low-pass filtering along the axon.

Features of sounds such as time and intensity are important binaural cues for localizing their sources. Interaural time differences (ITDs) and interaural level differences are extracted and processed in parallel by separate pathways in the brainstem auditory nuclei. ITD cues are small, particularly in small-headed animals, and processing of these cues is optimized by both morphological and physiological specializations. Moreover, recent observations in mammals and in some birds indicate that interaural time and level cues are not processed independently but cooperatively to improve the detection of interaural differences. This review will specifically summarize what is known about how inhibitory circuits improve the measurements of ITD in a sound-level-dependent manner.

Sound information is encoded as a series of spikes of the auditory nerve fibers (ANFs), and then transmitted to the brainstem auditory nuclei. Features such as timing and level are extracted from ANFs activity and further processed as the interaural time difference (ITD) and the interaural level difference (ILD), respectively. These two interaural difference cues are used for sound source localization by behaving animals. Both cues depend on the head size of animals and are extremely small, requiring specialized neural properties in order to process these cues with precision. Moreover, the sound level and timing cues are not processed independently from one another. Neurons in the nucleus angularis (NA) are specialized for coding sound level information in birds and the ILD is processed in the posterior part of the dorsal lateral lemniscus nucleus (LLDp). Processing of ILD is affected by the phase difference of binaural sound. Temporal features of sound are encoded in the pathway starting in nucleus magnocellularis (NM), and ITD is processed in the nucleus laminaris (NL). In this pathway a variety of specializations are found in synapse morphology, neuronal excitability, distribution of ion channels and receptors along the tonotopic axis, which reduces spike timing fluctuation in the ANFs-NM synapse, and imparts precise and stable ITD processing to the NL. Moreover, the contrast of ITD processing in NL is enhanced over a wide range of sound level through the activity of GABAergic inhibitory systems from both the superior olivary nucleus (SON) and local inhibitory neurons that follow monosynaptic to NM activity.

Deprivation of afferent inputs in neural circuits leads to diverse plastic changes in both pre- and postsynaptic elements that restore neural activity. The axon initial segment (AIS) is the site at which neural signals arise, and should be the most efficient site to regulate neural activity. However, none of the plasticity currently known involves the AIS. We report here that deprivation of auditory input in an avian brainstem auditory neuron leads to an increase in AIS length, thus augmenting the excitability of the neuron. The length of the AIS, defined by the distribution of voltage-gated Na super(+) channels and the AIS anchoring protein, increased by 1.7 times in seven days after auditory input deprivation. This was accompanied by an increase in the whole-cell Na super(+) current, membrane excitability and spontaneous firing. Our work demonstrates homeostatic regulation of the AIS, which may contribute to the maintenance of the auditory pathway after hearing loss. Furthermore, plasticity at the spike initiation site suggests a powerful pathway for refining neuronal computation in the face of strong sensory deprivation.

The electrical properties of rat Purkinje cells and synapses from granule cells were studied in dissociated cell cultures. To identify the cells we used an immunohistochemical method and recorded voltage-gated and synaptic currents with the patch-clamp technique (the whole-cell mode). Cultured Purkinje cells generated action potentials similar to those recorded from in vitro slices or in vivo preparations. Early Na, late Ca inward current, and K outward currents were distinguished by ion substitution under voltage clamp. We also recorded spontaneous synaptic currents in Purkinje cells cultured with granule cells. These synaptic currents reversed direction at the membrane potential of 2.5 mV, which was similar to currents induced by L-glutamate. Therefore, these are most likely excitatory synaptic currents from granule cells. Since these properties of Purkinje cells examined here are similar to those in situ, the cells in dissociated cell cultures offer a great opportunity to study biophysical properties of identified neurons in the central nervous system.

Properties of mechanoelectrical transduction were studied at the single-cell level by applying a whole-cell recording variation of the patch-clamp technique to dissociated vestibular hair cells of chicks. The hair bundle was directly stimulated by a glass rod, and transduction currents were recorded from the cell body. After a triangular movement of the stimulating probe, the transduction current was generated stepwise between discrete levels of amplitude. The minimum step amplitude was -1.8 pA at -27 mV in Na-containing normal saline.

The developmental time course of posttetanic potentiation was studied at an identified chemical synapse. In stage 11 juveniles (3 weeks after metamorphosis), the synaptic connections made by cholinergic neuron L$_{10}$ onto postsynaptic neurons L$_{2}$ to L$_{6}$ were present but showed no posttetanic potentiation. In stage 13 adults (12 weeks after metamorphosis), the same tetanus resulted in an increase of 300 percent in the synaptic potential. A similar pattern was observed at two other identified synapses in the abdominal ganglion. Thus, the initial steps in synapse formation do not include the expression of this plastic capability. Rather, at least 10 weeks is required between the onset of synaptic function and the final expression of mature synaptic properties.

The developmental time course of posttetanic potentiation was studied at an identified chemical synapse. In stage 11 juveniles (3 weeks after metamorphosis), the synaptic connections made by cholinergic neuron L 10 onto postsynaptic neurons L 2 to L 6 were present but showed no posttetanic potentiation. In stage 13 adults (12 weeks after metamorphosis), the same tetanus resulted in an increase of 300 percent in the synaptic potential. A similar pattern was observed at two other identified synapses in the abdominal ganglion. Thus, the initial steps in synapse formation do not include the expression of this plastic capability. Rather, at least 10 weeks is required between the onset of synaptic function and the final expression of mature synaptic properties.