Neuropeptide Modulation in Central Nervous System Dynamics

Neuropeptides form a versatile class of endogenous signalling molecules that fine-tune neuronal excitability, synaptic transmission and network rhythms throughout the central nervous system. Synthesised as precursor proteins and released in response to sustained or high-frequency activity, they act predominantly through G-protein-coupled receptors to initiate intracellular cascades that shape short- and long-term synaptic plasticity, circuit stability and behavioural state. Prominent examples—such as pituitary adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y and substance P—regulate arousal, stress responsiveness and mood, while also mediating neuroprotective and regenerative processes. By modulating the balance of excitation and inhibition across large-scale networks (including the default mode, salience and executive networks), neuropeptides influence cognitive flexibility, vigilance and emotional tone. Dysregulation of peptidergic signalling has been linked to neuropsychiatric and neurodegenerative conditions, prompting efforts to exploit receptor-selective agonists, peptidomimetics and advanced delivery routes for therapeutic intervention. Recent methodological advances—spanning genetic models, high-resolution imaging and novel administration techniques—have deepened our understanding of how neuropeptide dynamics underpin both healthy brain function and disease mechanisms.

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Neuropeptide Modulation in Central Nervous System Dynamics publication trend

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Technical terms

Neuropeptide: A short chain of amino acids released by neurons to modulate synaptic and network activity.

Neuromodulation: Regulation of neuronal and synaptic function by agents that alter the strength or kinetics of neurotransmission.

Synaptic plasticity: The capacity of synapses to strengthen or weaken over time in response to activity patterns.

Default mode network: A set of brain regions active during rest and internal thought, often modulated by neuropeptidergic signalling.

Intranasal delivery: Administration of substances through the nasal cavity to achieve central nervous system targeting.

G-protein-coupled receptor (GPCR): A membrane receptor that activates intracellular G-proteins in response to ligand binding, mediating peptidergic effects.

References

1. Circulating PACAP levels are associated with increased amygdala-default mode network resting-state connectivity in posttraumatic stress disorder. Neuropsychopharmacology (2023).
2. The Potential of the Nose-to-Brain Delivery of PACAP for the Treatment of Neuronal Disease. Pharmaceutics (2023).
3. Molecular and cellular correlates of human nerve regeneration: ADCYAP1/PACAP enhance nerve outgrowth. Brain (2020).