Specific Early and Late Oddball-Evoked Responses in Excitatory and Inhibitory Neurons of Mouse Auditory Cortex

A major challenge for sensory processing in the brain is considering stimulus context, such as stimulus probability, which may be relevant for survival. Excitatory neurons in auditory cortex, for example, adapt to repetitive tones in a stimulus-specific manner without fully generalizing to a low-probability deviant tone (oddball) that breaks the preceding regularity. Whether such stimulus-specific adaptation (SSA) also prevails in inhibitory neurons and how it might relate to deviance detection remains elusive. We obtained whole-cell recordings from excitatory neurons and somatostatin-and parvalbumin-positive GABAergic interneurons in layer 2/3 of mouse auditory cortex and measured tone-evoked membrane potential responses. All cell types displayed SSA of fast (early) subthreshold and suprath-reshold responses with oddball tones of a deviant frequency eliciting enlarged responses compared with adapted standards. SSA was especially strong when oddball frequency matched neuronal preference. In addition, we identified a slower late response component (200-400 ms after tone onset), most clearly in excitatory and parvalbumin-positive neurons, which also displayed SSA. For excitatory neurons, this late component reflected genuine deviance detection. Moreover, intracellular blockade of NMDA receptors reduced early and late responses in excitatory but not parvalbumin-positive neurons. The late component in excitatory neurons thus shares time course, deviance detection, and pharmacological features with the deviant-evoked event-related potential known as mismatch negativity (MMN) and provides a potential link between neuronal SSA and MMN. In summary, our results suggest a two-phase cortical activation upon oddball stimulation, with oddball tones first reactivating the adapted auditory cortex circuitry and subsequently triggering delayed reverberating network activity.