ÆVIANTBiosciences

Tonic and phasic signalling

Ongoing tonic activity and transient phasic responses vary with vigilance, sensory events, task state, and experimental context. This review describes the underlying observations and why they do not establish a pharmacological outcome for AVX-1.

This review is classified as preclinical evidence and was last reviewed July 16, 2026.

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. They do not establish how AVX-1 will behave.

Program boundary

Evidence context. Requires validation.

Preservation of phasic signalling and appropriate control of tonic activity are AVX-1 design objectives. They are not demonstrated properties.

No AVX-1 assay, functional study, in vivo study, or translational study has been completed. Computational work can generate and prioritize hypotheses, but it is not evidence that a molecule binds or works in a living system.

Limitations

The cited work includes correlational recordings, computational modelling, anaesthetized preparations, and imposed optogenetic activity. It does not prove that a drug will preserve, restore, or improve endogenous signalling dynamics.

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.

References and supporting evidence

The following records provide the principal public evidence used in this review. Their classifications and limitations remain part of the interpretation.

Locus coeruleus neurons can exhibit transient stimulus responses

Extracellular recordings in behaving rats identified short-latency transient responses to non-noxious environmental stimuli whose magnitude varied with vigilance.

Classification. Preclinical evidence.

Relevance to Aeviant. These observations support treating noradrenergic signalling as temporally structured rather than as a single static output.

Limitations. The study is correlational, uses rats, and does not establish a universal account of attention, salience, or therapeutic modulation.

  1. Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli — Aston-Jones G, Bloom FE, Journal of Neuroscience, 1981.

Tonic and phasic activity relate to behavioural context

Nonhuman-primate recordings associated changes in ongoing locus coeruleus activity and transient responses with vigilance and task state.

Classification. Preclinical evidence.

Relevance to Aeviant. The literature motivates explicit evaluation of timing and state when interpreting noradrenergic interventions.

Limitations. These are observational and modelling studies. Tonic and phasic activity should not be reduced to a simple pathological-versus-beneficial binary.

  1. Locus coeruleus activity in monkey: phasic and tonic changes are associated with altered vigilance — Rajkowski J, Kubiak P, Aston-Jones G, Brain Research Bulletin, 1994.
  2. The role of locus coeruleus in the regulation of cognitive performance — Usher M et al., Science, 1999.

Experimental locus coeruleus activation can produce frequency-dependent effects

Optogenetic work in mice demonstrated a causal relationship between imposed locus coeruleus firing patterns and measures of cortical activity and arousal.

Classification. Preclinical evidence.

Relevance to Aeviant. The study illustrates that timing and pattern can matter to system-level consequences.

Limitations. Optogenetic stimulation can be nonphysiological. Mouse arousal findings do not establish human efficacy or show that any drug preserves endogenous dynamics.

  1. Tuning arousal with optogenetic modulation of locus coeruleus neurons — Carter ME et al., Nature Neuroscience, 2010.
  2. Phasic locus coeruleus activity regulates cortical encoding of salience information — Vazey EM, Moorman DE, Aston-Jones G, PNAS, 2018.

Further reading: Noradrenergic regulation, the evidence library, and AVX-1.