Nonoverlapping Sets of Synapses Drive On Responses and Off Responses in Auditory Cortex

Abstract

SUMMARY Neurons in visual, somatosensory, and auditory cortex can respond to the termination as well as the onset of a sensory stimulus. In auditory cortex, these off responses may underlie the ability of the auditory system to use sound offsets as cues for perceptual grouping. Off responses have been widely proposed to arise from postinhibitory rebound, but this hypothesis has never been directly tested. We used in vivo whole-cell recordings to measure the synaptic inhibition evoked by sound onset. We find that inhibition is invariably transient, indicating that off responses are not caused by post-inhibitory rebound in auditory cortical neurons. Instead, on and off responses appear to be driven by distinct sets of synapses, because they have distinct frequency tuning and different excitatory-inhibitory balance. Furthermore, an on-on sequence causes complete forward suppression, whereas an off-on sequence causes no suppression at all. We conclude that on and off responses are driven by largely nonoverlapping sets of synaptic inputs.

Mind the Gap: Two Dissociable Mechanisms of Temporal Processing in the Auditory System

“…The number, location, and hemisphere of the ectopia were recorded. Consistent with previous reports (Sherman et al, 1987(Sherman et al, , 1990, nearly half the BXSB/MpJ-Yaa animals had ectopias, usually only one, located in the frontal cortex.…”

“…The model incorporates two key assumptions: (1) that auditory processing involves intensity gain control; and (2) that auditory thalamic population activity can be modeled as a weighted sum of outputs from two dissociable auditory channels, one most sensitive to sound onsets and another most sensitive to sound offsets. The idea that onset-sensitive and offset-sensitive central auditory pathways are dissociable is consistent with results of previous physiological investigations (He, 2001;Scholl et al, 2010;Kopp-Scheinpflug et al, 2011) as well as with our findings in BXSB/MpJYaa mice. Intensity gain control has also been reported in many previous studies of central auditory processing (Robinson and McAlpine, 2009) and is essential in the model to ensure that offset responses are evoked primarily following prolonged sounds, not following acoustic transients such as clicks (see Materials and Methods).…”

“…Ectopic and nonectopic BXSB/MpJ-Yaa mice are male littermates of an inbred mouse strain; the ectopias are thought to be a lowpenetrance consequence of genetic susceptibility to developmental disorders common to all inbred BXSB/MpJ-Yaa animals but expressed only stochastically or when triggered by environmental factors (Sherman et al, 1987(Sherman et al, , 1990. Therefore, comparisons made in this study are not between mutant and wild-type mice, but between genetically similar same-sex littermates of the same inbred strain, with or without a low-penetrance phenotypic abnormality (a cortical ectopia).…”

“…All BXSB/MpJ-Yaa mice have autoimmune disease (Andrews et al, 1978), which in humans has been linked with a high incidence of auditory temporal processing abnormalities and gap-detection deficits (Benasich, 2002;Bruner et al, 2009). Approximately 30%-50% of BXSB/MpJ-Yaa mice also have localized disruptions of neocortical lamination (ectopias) (Sherman et al, 1987(Sherman et al, , 1990, which resemble those observed in humans with auditory processing and developmental language disorders (Galaburda et al, 1985;Kaufmann and Galaburda, 1989;Ramus, 2004;Boscariol et al, 2011). Intriguingly, although the ectopias occur in frontal cortex and not in auditory cortex, ectopic BXSB/MpJ-Yaa mice have greater difficulty than their nonectopic littermates with behavioral tasks involving detection of brief gaps in noise (Clark et al, 2000b).…”

Sound offset-related brain potentials show retained sensory processing, but increased cognitive control activity in older adults

“…Neural responses to offsets have been identified in animal studies at all stages of the auditory pathway from the cochlear nucleus (e.g., Suga, 1964), to the auditory thalamus (He, 2001(He, , 2002 and the auditory cortex (e.g., Fishman and Steinschneider, 2009;Qin et al, 2007;Recanzone, 2000; for a recent overview, see Ramamurthy and Recanzone, 2017). It has also been shown that onset and offset responses in the auditory cortex -even if produced by the same neurons -are likely driven by separate sets of synapses (Scholl et al, 2010;O'Connell et al, 2011).…”