HYMNS · Hypothalamic Modulation of Neocortical States
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-01-01 → 2024-07-29
- EU contribution
- €278,841
- Participants
- 3
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Hypothalamic Modulation of Neocortical States
The neocortex is extensively regulated by neuromodulatory systems that release neurotransmitters, neuropeptides, and hormones to shape neuronal excitability and synaptic transmission. Key neuromodulators—including histamine (HA), acetylcholine, noradrenaline, dopamine, and serotonin—originate from subcortical nuclei and fine-tune cortical activity, playing essential roles in cognition and behavior. These systems regulate transitions between cognitive states by influencing cortical oscillations, such as gamma rhythms (30–80 Hz), which are crucial for attention, learning, and memory. Histamine, released by tuberomammillary nucleus (TMN) neurons, modulates cortical states and rhythmic network activity, with elevated HA levels correlating with gamma oscillations and cognitive function, though its precise mechanisms remain unclear. Dysregulated HA signaling is linked to neurological disorders like Alzheimer’s, Parkinson’s, and schizophrenia, contributing to cognitive deficits and disrupted neural dynamics. Given the €200 billion annual cost of neurodegenerative diseases in Europe, understanding HA’s role in neocortical circuits has significant therapeutic potential. HYMNS aims to systematically decode HA’s influence on cortical function, providing insights for both fundamental neuroscience and translational research.
Data: CORDIS, © European Union
Project objective
The neocortex is densely innervated by neuromodulatory systems that act through the release of hormones, neuropeptides, and neurotransmitters such as histamine (HA), acetylcholine (ACh), noradrenaline (NA), dopamine (DA), and serotonin (5-HT), which modulate cortical function by diffusely targeting neurons and synapses in neural microcircuits. These neuromodulators regulate shifts between behavioral states such as sleep and wakefulness, or distraction and attention by controlling rhythmic network activity. It is thought that neuromodulators regulate rhythmic activity by controlling the intrinsic characteristics of neuronal networks across different organizational levels – dendritic properties, cellular physiology, synaptic plasticity, and microcircuit dynamics. Recent work has demonstrated that high-frequency “gamma” oscillations (30-80 Hz), which crucially subserve cognitive processes such as attention, learning and memory, are associated with an increase in HA levels in subcortical regions. Altered levels of HA in the neocortex and dysfunction of its receptors have been implicated in the onset of Alzheimer’s and Parkinson’s disease – pathologies whose economic cost to Europe has been estimated at about € 200 billion per year. Despite the importance of HA in brain function and dysfunction, the mechanisms through which it controls neuronal, synaptic, dendritic, and microcircuit activity in the neocortex are unknown. Therefore, the objective of the HYMNS project is to employ an innovative combination of experiments and computational modelling to provide a unifying view of the mechanisms by which HA enables rhythmic microcircuit activity by controlling different organizational levels in the neocortex. The novel methods established in HYMNS will be useful not only for studies of HA but also for future investigations of other neuromodulators.
Original text from CORDIS.
Participants
- UNIVERSITY OF NEWCASTLE UPON TYNE · Newcastle Upon TyneCoordinatorUnited Kingdom
- MASSACHUSETTS INSTITUTE OF TECHNOLOGY · CambridgeUnited States
- UNIVERSITAET BERN · BernSwitzerland
Links
Data: CORDIS, © European Union