Abstract
In the neocortex, neuronal processing of sensory events is significantly influenced by context. For instance, responses in sensory cortices are suppressed to repetitive or redundant stimuli, a phenomenon termed “stimulus-specific adaptation” (SSA). However, in a context in which that same stimulus is novel, or deviates from expectations, neuronal responses are augmented. This augmentation is termed “deviance detection” (DD). This contextual modulation of neural responses is fundamental for how the brain efficiently processes the sensory world to guide immediate and future behaviors. Notably, context modulation is deficient in some neuropsychiatric disorders such as schizophrenia (SZ), as quantified by reduced “mismatch negativity” (MMN), an electroencephalography waveform reflecting a combination of SSA and DD in sensory cortex. Although the role of NMDA-receptor function and other neuromodulatory systems on MMN is established, the precise microcircuit mechanisms of MMN and its underlying components, SSA and DD, remain unknown. When coupled with animal models, the development of powerful precision neurotechnologies over the past decade carries significant promise for making new progress into understanding the neurobiology of MMN with previously unreachable spatial resolution. Currently, rodent models represent the best tool for mechanistic study due to the vast genetic tools available. While quantifying human-like MMN waveforms in rodents is not straightforward, the “oddball” paradigms used to study it in humans and its underlying subcomponents (SSA/DD) are highly translatable across species. Here we summarize efforts published so far, with a focus on cortically measured SSA and DD in animals to maintain relevance to the classically measured MMN, which has cortical origins. While mechanistic studies that measure and contrast both components are sparse, we synthesize a potential set of microcircuit mechanisms from the existing rodent, primate, and human literature. While MMN and its subcomponents likely reflect several mechanisms across multiple brain regions, understanding fundamental microcircuit mechanisms is an important step to understand MMN as a whole. We hypothesize that SSA reflects adaptations occurring at synapses along the sensory-thalamocortical pathways, while DD depends on both SSA inherited from afferent inputs and resulting disinhibition of non-adapted neurons arising from the distinct physiology and wiring properties of local interneuronal subpopulations and NMDA-receptor function.
Highlights
Organisms are continuously inundated with sensory information
This review aims to examine recent studies regarding the mechanisms of stimulus-specific adaptation (SSA) and deviance detection (DD) in animals and, when appropriate, compare them to human studies of mismatch negativity” (MMN)
Methods of interneuron silencing are important to consider as optogenetic suppression offers temporally precise and highly transient inactivation of desired cells, while chemogenetic suppression lasts several minutes to hours. This methodological difference means that chemogenetic suppression may affect all aspects of the oddball paradigm, affecting the overall encoding of the context or even giving rise to an adaptive rebalancing of inhibition/excitation ratios, for instance, while optogenetic suppression can be induced at discrete phases of the paradigm, which could contribute to the differences reported here
Summary
Organisms are continuously inundated with sensory information. Given that the majority of incoming information is redundant or behaviorally unimportant, organisms need to be able to suppress the neural processing of irrelevant stimuli to conserve resources. Because the correspondence of mouse responses to human-like MMN potentials measured at the scalp is unclear, animal studies of MMN-like processing have been typically held to the additional criterion of differentiating true DD from SSA (Harms et al, 2016) As described above, this requires at least two additional stimulus presentation paradigms, the flip flop and the many-standards paradigm (Figure 1; Hamm and Yuste, 2016), enabling the researcher to separate DD in a neuron’s augmented response to the ‘‘oddball’’ from its simple preference to that stimulus and the absence of SSA (Harms et al, 2016). It remains unknown whether SSA and DD are distinct processes and whether they are dependent on one another—in other words, must a neuronal circuit undergo adaptation to detect deviations from previous stimulation, and vice versa, is DD necessary for maintaining stimulus adaptation?
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