Activity‐dependent synaptic integration and modulation of bilateral excitatory inputs in an auditory coincidence detection circuit

Abstract

Neurons in the avian nucleus laminaris (NL) receive bilateral excitatory inputs from the cochlear nucleus magnocellularis, via morphologically symmetrical dorsal (ipsilateral) and ventral (contralateral) dendrites. Using in vitro whole-cell patch recordings in chicken brainstem slices, we investigated synaptic integration and modulation of the bilateral inputs to NL under normal and hearing deprivation conditions. We found that the two excitatory inputs onto single NL neurons were nearly completely segregated, and integration of the two inputs was linear for EPSPs. The two inputs had similar synaptic strength, kinetics and short-term plasticity. EPSCs in low but not middle and high frequency neurons were suppressed by activation of group I and II metabotropic glutamate receptors (mGluR I and II), with similar modulatory strength between the ipsilateral and contralateral inputs. Unilateral hearing deprivation by cochlea removal reduced the excitatory transmission on the deprived dendritic domain of NL. Interestingly, EPSCs evoked at the deprived domain were modulated more strongly by mGluR II than at the counterpart domain that received intact input in low frequency neurons, suggesting anti-homeostatic regulation. This was supported by a stronger expression of mGluR II protein on the deprived neuropils of NL. Under mGluR II modulation, EPSCs on the deprived input show transient synaptic facilitation, forming a striking contrast with normal hearing conditions under which pure synaptic depression is observed. These results demonstrate physiological symmetry and thus balanced bilateral excitatory inputs to NL neurons. The activity-dependent anti-homeostatic plasticity of mGluR modulation constitutes a novel mechanism regulating synaptic transmission in response to sensory input manipulations.

Why is the perceptual octave stretched? An account based on mismatched time constants within the auditory brainstem

“…1. Such a mechanism has been hypothesized within the medial superior olive (MSO) in a circuit that estimates interaural time differences (van der Heijden et al, 2013; Lu et al, 2018).…”

Why is the perceptual octave stretched? An account based on mismatched time constants within the auditory brainstem

“…1. Such a mechanism may be at work within the medial superior olive (MSO) in a circuit that estimates interaural time differences (van der Heijden et al, 2013;Lu et al, 2018).…”

Neuromodulation by mGluRs in Sound Localization Circuits in the Auditory Brainstem

“…The nucleus laminaris (NL), the avian equivalent of MSO in mammals, receives bilateral excitatory inputs from the NM. These two excitatory inputs are morphologically and physiologically symmetrical (Lu et al, 2018 ). While the NA is tasked with intensity (ILD) cues, NM and NL circuits process temporal (ITD) characteristics.…”

“…Given the symmetrical bilateral excitatory inputs each NL neuron receives from the two ears, the NL serves as an excellent model to address possible plasticity of mGluR modulation. After removing the cochlea from one ear, we witnessed a dramatic reduction of evoked EPSCs and surprisingly a selective increase in group II mGluR expression and physiological suppression of the excitatory input from the deafferented pathway (Lu et al, 2018 ). The results suggest that unilateral cochlear ablation disrupts the animal’s binaural processing capacity, and the upregulation of mGluRs modulation over eEPSCs presents an interesting case of anti-homeostatic plasticity.…”