The acoustic environment contains biologically relevant information on time scales from microseconds to tens of seconds. The auditory brainstem nuclei process this temporal information through parallel pathways that originate in the cochlear nucleus from different classes of cells. While the roles of ion channels and excitatory synapses in temporal processing have been well studied, the contribution of inhibition is less well understood. Here, we show in CBA/CaJ mice that the two major projection neurons of the ventral cochlear nucleus, the bushy and T-stellate cells, receive glycinergic inhibition with different synaptic conductance time courses. Bushy cells, which provide precisely timed spike trains used in sound localization and pitch identification, receive slow inhibitory inputs. In contrast, T-stellate cells, which encode slower envelope information, receive inhibition that is eight-fold faster. Both types of inhibition improved the precision of spike timing, but engage different cellular mechanisms and operate on different time scales. Computer models reveal that slow IPSCs in bushy cells can improve spike timing on the scale of tens of microseconds. While fast and slow IPSCs in T-stellate cells improve spike timing on the scale of milliseconds, only fast IPSCs can enhance the detection of narrowband acoustic signals in a complex background. Our results suggest that target-specific IPSC kinetics are critical for the segregated parallel processing of temporal information from the sensory environment.

Key points Sound information is transmitted by different subtypes of spiral ganglion neurons (SGN) from the ear to the brain. Selective damage of SGN peripheral synapses (cochlear synaptopathy) is widely recognized as one of the primary mechanisms of hearing loss, whereas the mechanisms at the SGN central synapses remain unclear. We report that different subtypes of SGN central synapses converge at different ratios onto individual target cochlear nucleus neurons with distinct physiological properties, and show biased morphological and physiological changes during age‐related hearing loss (ARHL). The results reveal a new dimension in cochlear nucleus neural circuitry that systematically reassembles and processes auditory information from different SGN subtypes, which is altered during ageing and probably contributes to the development of ARHL. In addition to known cochlear synaptopathy, the present study shows that SGN central synapses are also pathologically changed during ageing, which collectively helps us better understand the structure and function of SGNs during ARHL. Abstract Sound information is transmitted from the cochlea to the brain by different subtypes of spiral ganglion neurons (SGN), which show varying degrees of vulnerability under pathological conditions. Selective cochlear synaptopathy, the preferential damage of certain subtypes of SGN peripheral synapses, has been recognized as one of the main mechanisms of hearing loss. The organization and function of the auditory nerve (AN) central synapses from different subtypes of SGNs remain unclear, including how different AN synapses reassemble onto individual neurons in the cochlear nucleus, as well as how they differentially change during hearing loss. Combining immunohistochemistry with electrophysiology, we investigated the convergence pattern and subtype‐specific synaptopathy of AN synapses at the endbulb of Held, as well as the response properties of their postsynaptic bushy neurons in CBA/CaJ mice of either sex under normal hearing and age‐related hearing loss (ARHL). We found that calretinin‐expressing (type Ia) and non‐calretinin‐expressing (type Ib/Ic) endbulbs converged along a continuum of different ratios onto individual bushy neurons with varying physiological properties. Endbulbs degenerated during ageing in parallel with ARHL. Furthermore, the degeneration was more severe in non‐calretinin‐expressing synapses, which correlated with a gradual decrease in bushy neuron subpopulation predominantly innervated by these inputs. These synaptic and cellular changes were profound in middle‐aged mice when their hearing thresholds were still relatively normal and prior to severe ARHL. Our findings suggest that biased AN central synaptopathy and the correlated shift in cochlear nucleus neuronal composition play significant roles in weakened auditory input and altered central auditory processing during ARHL.

Xie, Ruili, John Meitzen, and George D. Pollak. Differing roles of inhibition in hierarchical processing of species-specific calls in auditory brainstem nuclei. J Neurophysiol 94: 4019 -4037, 2005. First published August 31, 2005 doi:10.1152/jn.00688.2005. Here we report on response properties and the roles of inhibition in three brain stem nuclei of Mexican-free tailed bats: the inferior colliculus (IC), the dorsal nucleus of the lateral lemniscus (DNLL) and the intermediate nucleus of the lateral lemniscus (INLL). In each nucleus, we documented the response properties evoked by both tonal and speciesspecific signals and evaluated the same features when inhibition was blocked. There are three main findings. First, DNLL cells have little or no surround inhibition and are unselective for communication calls, in that they responded to ϳ97% of the calls that were presented. Second, most INLL neurons are characterized by wide tuning curves and are unselective for species-specific calls. The third finding is that the IC population is strikingly different from the neuronal populations in the INLL and DNLL. Where DNLL and INLL neurons are unselective and respond to most or all of the calls in the suite we presented, most IC cells are selective for calls and, on average, responded to ϳ50% of the calls we presented. Additionally, the selectivity for calls in the majority of IC cells, as well as their tuning and other response properties, are strongly shaped by inhibitory innervation. Thus we show that inhibition plays only limited roles in the DNLL and INLL but dominates in the IC, where the various patterns of inhibition sculpt a wide variety of emergent response properties from the backdrop of more expansive and far less specific excitatory innervation.

Tuning curves were recorded with patch electrodes from the inferior colliculus (IC) of awake bats to evaluate the tuning of the inputs to IC neurons, reflected in their synaptic tuning, compared with the tuning of their outputs, expressed in their discharge tuning. A number of unexpected features were revealed with whole-cell recordings. Among these was that most neurons responded to tones with inhibition and/or subthreshold excitation over a surprisingly broad frequency range. The synaptic tuning in many cells was at least 1.5-2.0 octaves wide and, on average, was more than twice as wide as the frequency range that evoked discharges even after inhibition was blocked. In most cells, tones evoked complex synaptic response configurations that varied with frequency, suggesting that these cells were not innervated by congruent excitatory and inhibitory projections. Synaptic tuning was not only wide but was also diverse, in which some cells were dominated by excitation (n ϭ 20), others were dominated by excitation with sideband inhibition (n ϭ 21), but most were dominated by inhibition with little evidence of excitation (n ϭ 31). Another unexpected finding was that some cells responded with inhibition to the onset and offset of tones over a wide frequency range, in which the patterns of synaptic responses changed markedly with frequency. These cells never fired to tones at 50 dB sound pressure level but fired to frequency-modulated sweeps at that intensity and were directionally selective. Thus, the features revealed by whole-cell recordings show that the processing in many IC cells results from inputs spectrally broader and more complex than previously believed.

Alkynoates are added to aromatic and α,β‐unsaturated aldehydes in the synthesis of the title compounds in optically active form. This highly enantioselective and useful method is carried out under mild reaction conditions and employs the readily available chiral 1,1′‐bi‐2‐naphthol (binol) ligand and the metal reagents Et2Zn and [Ti(OiPr)4] (see scheme; HMPA=hexamethylphosphoramide).