Navegando por Autor "Walmsley, Bruce"
Agora exibindo 1 - 2 de 2
- Resultados por página
- Opções de Ordenação
Artigo Lateral superior olive function in congenital deafness(2011-01-27) Couchman, Kiri; Garrett, Andrew; Deardorff, Adam S.; Rattay, Frank; Resatz, Susanne; Fyffe, Robert; Walmsley, Bruce; Leão, Richardson NavesThe development of cochlear ilmplants for the treatment of patients with profound hearing loss has advanced considerably in the last few decades, particularly in the field of speech comprehension. However, attempts to provide not only sound decoding but also spatial hearing are limited by our understanding of circuit adaptations in the absence of auditory input. Here we investigate the lateral superior olive (LSO), a nucleus involved in interaural level difference (ILD) processing in the auditory brainstem using a mouse model of congenital deafness (the dn/dn mouse). An electrophysiological investigation of principal neurons of the LSO from the dn/dn mouse reveals a higher than normal proportion of single spiking (SS) neurons, and an increase in the hyperpolarisation-activated Ih current. However, inhibitory glycinergic input to the LSO appears to develop normally both pre and postsynaptically in dn/dn mice despite the absence of auditory nerve activity. In combination with previous electrophysiological findings from the dn/ dn mouse, we also compile a simple Hodgkin and Huxley circuit model in order to investigate possible computational deficits in ILD processing resulting from congenital hearing loss. We find that the predominance of SS neurons in the dn/dn LSO may compensate for upstream modifications and help to maintain a functioning ILD circuit in the dn/dn mouse. This could have clinical repercussions on the development of stimulation paradigms for spatial hearing with cochlear implants.Artigo Modulation of dendritic synaptic processing in the lateral superior olive by hyperpolarization-activated currents(2011-01-10) Leão, Emelie Katarina Svahn; Leão, Richardson Naves; Walmsley, BruceWe have previously shown that mice lateral superior olive (LSO) neurons exhibit a large hyperpolarization-activated current (Ih), and that hyperpolarization-activated cyclic-nucleotide-gated type 1 channels are present in both the soma and dendrites of these cells. Here we show that the dendritic Ih in LSO neurons modulates the integration of multiple synaptic inputs. We tested the LSO neuron’s ability to integrate synaptic inputs by evoking excitatory post-synaptic potentials (EPSPs) in conjunction with brief depolarizing current pulses (to simulate a second excitatory input) at different time delays. We compared LSO neurons with the native Ih present in both the soma and dendrites (control) with LSO neurons without Ih (blocked with ZD7288) and with LSO neurons with Ih only present perisomatically (ZD7288+ computer-simulated Ih using a dynamic clamp). LSO neurons without Ih had a wider time window for firing in response to inputs with short time separations. Simulated somatic Ih (dynamic clamp) could not reverse this effect. Blocking Ih also increased the summation of EPSPs elicited at both proximal and distal dendritic regions, and dramatically altered the integration of EPSPs and inhibitory post-synaptic potentials. The addition of simulated peri-somatic Ih could not abolish a ZD7288-induced increase of responsiveness to widely separated excitatory inputs. Using a compartmental LSO model, we show that dendritic Ih can reduce EPSP integration by locally decreasing the input resistance. Our results suggest a significant role for dendritic Ih in LSO neurons, where the activation ⁄ deactivation of Ih can alter the LSO response to synaptic inputs.