A fundamental question in neuroscience is how neurons perform precise operations despite inherent variability. low-voltage-activated potassium conductance (and and vs. = 0.01 level (Fisher 1995; Zahar et al. 2009). We also used a bootstrap Sipeimine procedure to compute 99% confidence intervals (bias corrected and accelerated) for vector strength estimates at 70 and 120 dB, separately, to gauge the reliability of the vector strength measure (error bars in Fig. 3and vs. < 0.01). In contrast, the neuron with < 0.01) vector strength across this same 50-dB range irrespective of auditory nerve fiber input type or mix, whereas with a static leak there was a significant drop of 0.12 to 0.22. Intensity-invariant spike-time precision is usually robust to changes in auditory nerve model parameters and requires and Fig. 2, and ?and3and and histogram: 0.97, 0.98, and 0.99). Most neurons maintained a similarly high level of precision at 120 dB SPL (histogram: 0.94, 0.97, and 0.98). Vector strengths at the two intensities were positively correlated; neurons at the lower end of the vector strength distribution at 80 dB were also at the lower end at 120 dB SPL. With and C) and susceptibility to changes in the number or strength of synaptic inputs when gKL was replaced with a static leak. Therefore, in theory, the present results could have been uncovered and reported exclusively using a software model. Subtypes of Bushy Cells and Cell-to-Cell Variance Throughout the results section we referred to the model generically as a bushy cell, but in fact there are two distinct subtypes of bushy cells, globular and spherical, that have different distributions of synaptic convergence and conductance magnitudes as well as distinct axonal targets (Smith et al. 1991, 1993). On average, globular bushy cells are innervated by more auditory nerve fibers than spherical cells. Anatomic measurements from cats indicate that globular bushy cells are innervated by between 9 and 69 somatic inputs, with a median of about 19 (Spirou et al. 2005), whereas spherical bushy cells are innervated by between 1 and 3 (Brawer and Morest 1975; Ryugo and Sento 1991). Physiological estimates from the mouse indicate that globular bushy cells receive four or more inputs, whereas spherical bushy cells receive three or fewer (Cao and Oertel 2010). The average size of auditory nerve boutons is usually smaller on globular bushy cell somas compared with spherical, suggesting Rabbit polyclonal to PAI-3 different effective strengths of each synapse. Globular bushy cells often have twofold greater gKL magnitude (Cao et al. 2007). Although there is usually significant variance in these parameters between cell types, there is usually also substantial variance Sipeimine of these (and other) parameters within cell types (Cao and Oertel 2010; Rothman and Manis 2003a). To test the effect of these differences on our model, we systematically varied the number of synaptic inputs and leak conductance magnitudes to encompass the variance observed within and between globular and spherical bushy cells (Fig. 6). In almost all conditions the model with gKL intact retained its intensity-invariant spike-time precision, which is usually consistent with the observation that a majority of both globular and spherical bushy cells exhibit this unique phenomenon. With gKL intact, the bushy cell’s response Sipeimine was insensitive to biophysical variance, as is usually sometimes seen in other neural circuits subject to variability (Prinz et al. 2003a). In contrast, with gKL replaced by a static leak, the bushy cell achieved intensity-invariant spike-time precision with only a few combinations of synaptic inputs and conductances. Such combinations are also observed in Sipeimine other neural circuits (Taylor et al. 2009), where desired neural responses are achieved with disparate mixtures of biophysical parameters. Some neural circuits maintain consistent functionality despite variability in a conductance’s magnitude by compensatory changes within a cell (Goaillard et al. 2009; MacLean et al. 2003) or across synapses within a local network (Grashow et al. 2010). We exhibited that gKL’s dynamics protect the bushy cell from heterogeneity without requiring homeostatic compensation of other conductances within the cell or synaptic changes within the local network. The protection extended to a large population of silicon neurons whose biophysical heterogeneity was emulated with transistor mismatch, therefore addressing a fundamental design constraint in neuromorphic engineering. Other gKL-Expressing Neurons The stability of the model’s response over such a wide range of acoustic and biophysical parameters suggests that other auditory neurons with gKL have the capacity for robust spike-time precision. Several cell types besides bushy cells possess gKL and have precisely timed spikes, including spiral ganglion cells of the auditory nerve Sipeimine (Adamson et al. 2002; Santos-Sacchi 1993), octopus cells of the cochlear nucleus (Bal and Oertel 2001),.