Brains@Bay Meetup: A Primer on Neuromodulatory Systems - Srikanth Ramaswamy
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Meetup page: https://www.meetup.com/Brains-Bay/events/284481247/ Neuromodulators are signalling chemicals in the brain, which control the emergence of adaptive learning and behaviour. Neuromodulators including dopamine, acetylcholine, serotonin and noradrenaline operate on a spectrum of spatio-temporal scales in tandem and opposition to reconfigure functions of biological neural networks and to regulate global cognition and state transition. Although neuromodulators are important in shaping cognition, their phenomenology is yet to be fully realized in deep neural networks (DNNs). In this talk, we will give an overview of the biological organizing principles of neuromodulators in adaptive cognition and highlight the competition and cooperation across neuromodulators.
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Brains@Bay Meetup: A Primer on Neuromodulatory Systems - Srikanth Ramaswamy
- 1. A primer on neuromodulatory systems Srikanth Ramaswamy, PhD Principal Investigator, Neural Circuits Laboratory
- 2. Motivation – the synaptic brain Credit: Scientopia Human brain: ~86 billion neurons (109) , ~100 trillion synapses (1012) Credit: Wikipedia
- 3. Neuromodulatory projections • Neuromodulation is the physiological process by which a given neuron uses one or more neurotransmitters to regulate diverse populations of neurons • Neuromodulators are neurotransmitters, neuropeptides, hormones that have spatially distributed, temporally extended effects on target neurons, synapses and microcircuits Ascending neuromodulatory systems • Cholinergic • Dopaminergic • Serotonergic • Adrenergic • Histaminergic Mei, Muller & Ramaswamy, 2022, Trends in Neurosciences
- 4. 55 morphological types in neocortical microcircuitry 3025 (552) possible m-type specific synaptic connections 1941 viable m-type specific synaptic connections Markram*, Muller*, Ramaswamy*, Reimann* et al. Cell, 2015 * Co first author
- 6. L23 PC L4 PC L5 PC L5a PC L6 PC L6b PC Acetylcholine Noradrenaline Serotonin Dopamine Adr 3 Htr1a Htr1b Htr1f Htr3b Htr4 Htr5a Htr5b Htr6 Htr7 Drd1 M1 M2 M3 M4 nAchR 1 nAchR 2 nAchR 3 nAchR 4 nAchR 5 nAchR 7 nAchR 1 nAchR 2 nAchR 3 Adr 1a Adr 1b Adr 2a Adr 2 Htr2a Htr2c Htr3a Adr 1 Drd5 Normalized Expression 0 1 Hrh1 Hrh2 Hrh3 Histamine Int2 Int3 Int5 Int6 Int7 Int12 Int14 Int15 Int8 Int13 Int11 Int9 Int10 Int1 Int16 Int4 Pvalb SST Calb1 Calb2 VIP NPY Diversity of receptors
- 7. Synaptic receptors Ionotropic receptors Credit: Purves, Augustine, Fitzpatrick et al.
- 8. Metabotropic receptors Credit: Purves, Augustine, Fitzpatrick et al. Synaptic receptors
- 10. Neuromodulatory systems regulate cortical states Adapted from Muñoz and Rudy, 2014
- 11. Towards a unifying view of neuromodulation
- 12. Multi-scale functions of neuromodulators
- 13. Teles-Grilo Ruivo and Mellor, 2013 Acetylcholine in the Hippocampus
- 14. Synaptic plasticity “Cells that fire together, wire together". Hebb’s postulate “When an axon of cell A is near enough to excite cell B or repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased”. Donald O. Hebb (1949)
- 15. Zhang et al. 2009 Spike-timing-dependent plasticity (STDP) is considered a physio- logically relevant form of Hebbian learning. However, behavioral learning often involves action of reinforcement or reward signals such as dopamine. Dopamine in the Hippocampus
- 16. Andersson et al. 2017 Andersson et al. 2017 Histamine in the Hippocampus
- 17. Functional diversity of neuromodulators •The same neuron can be targeted by multiple neuromodulators •Neuromodulators can produce qualitative changes in the intrinsic properties of neurons, e.g. transform tonic firing into phasic bursting •The same neuromodulators within a network can differetially regulate cell-types and their synaptic connections
- 18. Take-home organizing principles of neuromodulators • Most neuromodulatory systems project from sub-cortical regions • Neurons releasing specific neuromodulators are referred to as loci, which broadcast to larger areas within the brainstem, thalamus, and cortex • Most neuromodulatory systems are reciprocally connected with the frontal cortex and parts of the limbic system – that regulates behavioural and emotional responses • Neuromodulators function in co-operation or opposition to bring changes in brain states