Tonic and phasic signalling

Definitions

Evidence context. Established biology.

Tonic activity describes ongoing discharge across a period of time. Phasic responses describe transient changes associated with particular events or task conditions. Both vary across experimental and behavioural states.

These terms are descriptive. Neither is uniformly pathological or beneficial, and the boundary between them depends on how activity is measured and analysed.

Experimental and behavioural context

Evidence context. Preclinical evidence.

Recordings in rodents and nonhuman primates have associated changes in locus coeruleus activity with vigilance, sensory events, and task performance. Optogenetic studies provide causal evidence that different imposed activity patterns can produce different effects.

Those experiments support a limited conclusion: the consequences of perturbing a regulatory system can depend on timing and biological state. AVX-1 behaviour requires program-specific experimental measurement.

Program boundary

Evidence context. Requires validation.

Preservation of phasic signalling and appropriate control of tonic activity are AVX-1 design objectives requiring experimental evaluation.

Limitations

The cited work includes correlational recordings, computational modelling, anaesthetized preparations and imposed optogenetic activity. Drug effects on endogenous signalling dynamics require direct pharmacological evidence.

Relevance to the current program

Timing is part of Aeviant’s public interpretation of physiological selectivity. Whether AVX-1 retains endogenous timing is a program objective that requires experimental testing.

Evidence records

The Evidence Library contains the source, relevance and limitations for each record used in this review.

• Locus coeruleus neurons can exhibit transient stimulus responses — Preclinical evidence.
  1. Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli
• Tonic and phasic activity relate to behavioural context — Preclinical evidence.
  1. Locus coeruleus activity in monkey: phasic and tonic changes are associated with altered vigilance
  2. The role of locus coeruleus in the regulation of cognitive performance
• Experimental locus coeruleus activation can produce frequency-dependent effects — Preclinical evidence.
  1. Tuning arousal with optogenetic modulation of locus coeruleus neurons
  2. Phasic locus coeruleus activity regulates cortical encoding of salience information