Distinct neural firing mechanisms to tonal stimuli offset in the inferior colliculus of mice in vivo

Abstract

Offset neurons, which fire at the termination of sound, likely encode sound duration and serve to process temporal information. Offset neurons are found in most ascending auditory nuclei; however, the neural mechanisms that evoke offset responses are not well understood. In this study, we examined offset neural responses to tonal stimuli in the inferior colliculus (IC) in vivo with extracellular and intracellular recording techniques in mice. Based on peristimulus time histogram (PSTH) patterns, we classified extracellular offset responses into four types: Offset, Onset-Offset, Onset-Sustained-Offset and Inhibition-Offset types. Moreover, using in vivo whole-cell recording techniques, we found that offset responses were generated in most cells through the excitatory and inhibitory synaptic inputs. However, in a small number of cells, the offset responses were generated as a rebound to hyperpolarization during tonal stimulation. Many offset neurons fired robustly at a preferred duration of tonal stimulus, which corresponded with the timing of rich excitatory synaptic inputs. We concluded that most IC offset neurons encode the termination of the tone stimulus by responding to inherited ascending synaptic information, which is tuned to sound duration. The remainder generates offset spikes de novo through a post-inhibitory rebound mechanism.

The function of offset neurons in auditory information processing

“…Furthermore, evoked responses may be divided into onset response, offset response, onset-offset response, and sustained response, depending on the action potential (AP) firing triggered by the beginning or the end of the acoustic stimuli [31]. Different response patterns could represent distinct physiological implications [41], and have special local neuronal circuits [42].…”

“…Moreover, based on the pattern of peri-stimulus-time histograms (PSTH), the offset neurons can be classified into four types: offset, onset-offset, onset-sustained-offset, and inhibition-offset (Fig. 1) [31].…”

“…This tendency is applied to bats such as Rhinolophus megaphyllus, Rhinolophus philippinensis, Hipposideros diadema, Taphazous georgianu [52], Aseuiscus tricuspidatus [48], guinea pigs [24], rats [51], mice [31], as well as humans [53], but independent of recording methods. Using AEP recording, compared with the amplitude of onset response increasing monotonically with intensity elevation, the amplitude of offset ABR goes through a maximum [48], sometimes will reduce with further increase of stimulus intensity [54], while the number of action potentials (APs) continuously increases with sound intensity increasing in the superior paraolivary nucleus (SPON) of mice using single-unit recording [40], this discrepancy may be induced by the recording methods or the difference between nuclei because the ABR amplitude depend on the synchronization of neuron population and some neurons may change their discharge patterns with intensity changing.…”

“…Given that cells within the ventral nucleus of the lateral lemniscus (VNLL) respond to tones with a single precise onset response [90,91], and that SPON and VNLL neurons are respectively GABAergic and glycinergic, and both provide inhibition to the ipsilateral IC [92,93], the convergent inputs from SPON and VNLL to IC may explain the onset-offset responses with IPSPs both at the onset and offset of the tone in the auditory midbrain [94][95][96]. These speculations might suggest that offset neurons (except onset-sustainedoffset type) that arise de novo in some auditory nuclei maintain their original function, while some inherit ascending synaptic information [31], which also suggest that onset and offset responses may be encoded by distinct acoustic channels. This speculation is consistent with the study by He [20] for onset and offset pathway segregation in the auditory thalamus.…”

“…The origins of the asymmetries of psychophysics and neurophysiology have a common response threshold mechanism which adaptively tracks the ongoing level of stimulation [30]. For auditory processing and complex distinction, since sound duration is considered to be one of the essential information [31], offset responses encoding the sound termination may play an important role. As is well known, onset neurons respond to a stimulus but cannot distinguish the cessation of one [32].…”