Neuromodulation in cognition
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Neuromodulation involves neurotransmitters regulating diverse neuron populations. Several neuromodulatory systems project to brain regions involved in cognition, including the prefrontal cortex. These systems include cholinergic, dopaminergic, serotonergic, and noradrenergic projections. Cholinergic modulation is important for attention, working memory, and cue detection through muscarinic and nicotinic receptors. Experimental evidence shows cholinergic systems are required for cognitive functions. Neuromodulators can alter neuron properties and influence cognitive processes by increasing signal-to-noise ratios and biasing cortical processing.
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Neuromodulation in cognition
- 2. Overview • • • • • • What is Neuromodulation? How exactly the modulation is brought about? Brain regions involved in cognition Modulatory projections Cholinergic modulation Summary
- 3. Neuromodulation is the physiological process by which a given neuron uses one or more neurotransmitters to regulate diverse populations of neurons Neuromodulators are the neurotransmitters, neuropeptides, hormones that have spatially distributed, temporally extended effects on the recipient neurons and circuits.
- 4. Neuromodulatory systems Ascending neuromodulatory systems • Cholinergic • Dopaminergic • Serotonergic • Adrenergic Co-transmitters as neuromodulators Neuropeptides as neuromodulators Circulating hormones as Modulators
- 5. Architecture of the neuromodulatory systems. Jeffrey L. Krichmar, Adaptive Behavior 2008; 16; 385
- 6. K. Doya / Neural Networks 15 (2002) 495–50
- 7. Commonalities among neuromodulatory systems 1.The origination of these systems is sub-cortical. 2. Each of these neuromodulatory systems is the locus of a particular chemical transmitter that is projected to broad areas of the brainstem, thalamus, and cortex. 3. All of these neuromodulatory systems are reciprocally connected with the frontal cortex and parts of the limbic system.
- 8. Modes of modulation E. Marder, V. Thirumalai / Neural Networks 15 (2002) 479–493
- 9. E. Marder ;Neuron; 2012
- 10. Heterosynaptic facilitation Presynaptic inhibition Diffusely delivered modulator Postsynaptic can act on presynaptic receptors release mechanism E. Marder, V. Thirumalai / Neural Networks 15 (2002) 479–493
- 11. Crustacean models of neuromodulation E. Marder ;Neuron; 2012
- 12. Intrinsic properties of a model neuron with different balance of conductances. Activity patterns of pyloric neurons in the intact circuit and when isolated. E. Marder, V. Thirumalai / Neural Networks 15 (2002) 479–493
- 13. Alteration of intrinsic properties by neuromodulators • The same neuron can be the target of multiple modulatory Substances • Some modulators can produce qualitative changes in the intrinsic properties of neurons, e.g. transform a tonically firing neuron into a bursting neuron •modulators can influence the frequency of either tonic activity or bursting, and •Different cell types within a network can be influenced differentially by the same neuromodulatory substances. E. Marder ;Neuron76; 012
- 14. Effects of Modulatory Substances on a Membrane potential of Neuron E. Marder, V. Thirumalai / Neural Networks 15 (2002) 479–493
- 15. Co-existance with other modulators E. Marder, V. Thirumalai / Neural Networks 15 (2002) 479–493
- 16. Multiple Neuromodulators Can Activate Different Forms of the Pyloric Rhythm E. Marder, V. Thirumalai / Neural Networks 15 (2002) 479–493
- 17. Principles of neuromodulation • Modulators co-ordinately act on opposing processes • Voltage dependence of modulator actions • Convergence of many modulators onto the Same voltage-dependent current • Saturation of postsynaptic action: Bigger synaptic inputs produce larger effects on target neuron activity • Modulators act co-ordinately on multiple targets to keep systems functionally ‘‘Matched’’ Eve Marder , Neuron 2012
- 18. Coexistence of some neuropeptides and neurotransmitters in brain areas associated with cognitive functions. S.O. Ögren et al. / European Journal of Pharmacology 626 (2010) 9–17
- 19. Role of Prefrontal cortex in Cognition • • • • Working memory Behavioral inhibition Attentional processing Future planning
- 20. L.A. Briand et al. / Progress in Neurobiology; 83 (2007)
- 21. coronal sections from the macaque monkey PFC illustrating the relative densities of tyrosine hydroxylase (DA),dopamine-b-hydroxylase (NE), choline acetyltransferase (ChAT), and serotonin L.A. Briand et al. / Progress in Neurobiology; 83 (2007)
- 22. Principles of Neural science, Kandle and Shwartz,4th edition
- 23. Neuromodulatory systems projecting to PFC • • • • • • • Cholinergic system Serotonergic system Adrenergic system Dopaminergic system Histaminergic system Volume transmission Neuropeptides
- 24. Basal Forebrain and brainstem cholinergic projections Newman et al; June 2012; Frontiers in Behavioral Neuroscience;
- 25. Newman et al; June 2012; Frontiers in Behavioral Neuroscience;
- 27. Cholinergic receptors • Muscarinic receptors M1 & M2 M1 subtypes: m1, m3, m5 (Layer I, II) M2 subtypes: m2, m4 (Layer III, V ) • Nicotinic receptors α subunits (α2-10 ) β subunits (β 2-4 )
- 28. Principles of Neural science, Kandle and Shwartz,4th edition
- 29. Experimental evidences of modulation of cognitive functions • • • • Cholinotoxins: 192 IgG saporin Microdialysis studies Electrophysiological studies Pharmacological studies
- 30. Cued appetitive response task ME Hasselmo and M Sarter, NeuropsychopharmacologyREVIEWS(2011) 36, 52–73
- 31. • cholinergic system is required specifically for the detection of cues. • It increases the signal to noise ratio (Metherate & Ashe 1991)
- 32. Effect of Ach on LTP High Ach lowers the threshold for LTP induction. Heurta and Lisman 1993 Newman et al 2012; Frontiers in Behavioral Neuroscience
- 33. The Gestalt law of Visual Grouping and Acetylcholine
- 34. Acetylcholine contributes to attentional modulation and orientation selectivity in the primary visual cortex through mAChR. • Acetylcholine can boost neural signals in response to low contrast stimuli, through presynaptic nAChR mediated upregulation of Glutamate release. • Acetylcholine can bias cortical processing in favour of sub or intracortical inputs. •
- 35. Noradrenergic modulation of prefrontal cholinergic function Source: Locus cereoleus Receptors: α 1 & α 2 α 1 agonists increases Ach release α 2 agonists decreases Ach release Atomoxetine : NE reuptake inhibitor enhances Ach release Effect on basal forebrain: Depolarise cholinergic neurons L.A. Briand et al. / Progress in Neurobiology; 83 (2007)
- 36. Serotonergic modulation of prefrontal function Source : Dorsal raphe nucleus Receptors: 5-HT (1-7) subtypes 5-HT 2 Agonists increase Ach release 5-HT 3 Agonists decrease Ach release L.A. Briand et al. / Progress in Neurobiology; 83 (2007)
- 37. Dopaminergic modulation of prefrontal function Source: Ventral tegmental mesocortical neurons Receptors: D1,D2,D3 D1 Agonists increase Ach release D2 Agonists has no effect D3 Agonists decreases Ach release L.A. Briand et al. / Progress in Neurobiology; 83 (2007)
Editor's Notes
- Left, the AB neuron was isolated by photoinactivation of the PD neurons and by pharmacologicalblockade of all other chemical synaptic interactions. Right, the PD neurons were isolated by photoinactivation of the AB neuron and pharmacologicalblockadeof all other synaptic interactions. From top to bottom, the traces show the activity of isolated AB and PD neurons in control, in 1024M pilocarpine (amuscarinic agonist), 1024M dopamine and 1024M serotonin, respectively.
- The first experimentsusing this technique in task-performing animals used a cued appetitive response task to determine cholinergicactivity in the medial prefrontal cortex (mPFC) and acontrol region (forelimb region in the motor cortex). In thistask (for details see Parikh et al, 2007), animals werepresented with a rarely occurring cue that predictedsubsequent reward delivery at one out of two reward ports.Animals detected the majority of these cues, as indicated bycue-evoked disengagement from ongoing behavior (usuallygrooming), and orientation toward, and monitoring of, thereward ports (see Figure 1). Occasionally, cues did notevoke such behavior. Video tape-based inspection of theanimals’ behavior during trials involving such missesindicated a brief, cue-evoked orientation-like response that,however, was followed by an immediate return to groomingbehavior.
- Detection is defined as a cognitive process that involves the insertion of a cue into ongoing behavioral and cognitive activity and subsequent control of such behavior by the cue(Posneret al, 1980).
- The principle maintains that the human eye sees objects in their entirety before perceiving their individual parts, suggesting the whole is greater than the sum of its parts. Further, the whole is anticipated when the parts are not integrated or complete
- when delivered at the thalamocortical synapse in layer IV of the primary visualcortexHigh ACh is associated with domination of subcortical (thalamocortical) inputs and perception of parts, whereas low AChfavorsintracortical inputs and holistic perception.
- 5-HT1 receptors (1A, 1B, 1D, 1E,1F)5-HT2 receptors (2A, 2B, and 2C)- Increase Ach release5-HT5 receptors (5A and 5B)