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Neuromodualtors in Cognition
Vijaya Kumar
3-01-2014
Overview
• What is Neuromodulation?• How exactly the modulation is brought about?• Brain regions involved in cognition• Modulatory projections• Cholinergic modulation• Summary
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.
Neuromodulatory systems
Ascending neuromodulatory systems• Cholinergic• Dopaminergic• Serotonergic• AdrenergicCo-transmitters as neuromodulatorsNeuropeptides as neuromodulatorsCirculating hormones as Modulators
Architecture of the neuromodulatory systems.
Jeffrey L. Krichmar, Adaptive Behavior 2008; 16; 385
K. Doya / Neural Networks 15 (2002) 495–50
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.
Modes of modulation
E. Marder, V. Thirumalai / Neural Networks 15 (2002) 479–493
E. Marder ;Neuron; 2012
Heterosynaptic facilitation
Presynaptic inhibition
Diffusely delivered modulator can act on presynapticrelease mechanism
Postsynaptic receptors
E. Marder, V. Thirumalai / Neural Networks 15 (2002) 479–493
Crustacean models of neuromodulation
E. Marder ;Neuron; 2012
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
Alteration of intrinsic properties by neuromodulators• The same neuron can be the target of multiple modulatorySubstances• 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 anetwork can be influenced differentially by the same neuromodulatory substances.
E. Marder ;Neuron76; 012
Effects of Modulatory Substances on a Membrane potential of Neuron
E. Marder, V. Thirumalai / Neural Networks 15 (2002) 479–493
Co-existance with other modulators
E. Marder, V. Thirumalai / Neural Networks 15 (2002) 479–493
Multiple Neuromodulators Can Activate Different Forms of the Pyloric Rhythm
E. Marder, V. Thirumalai / Neural Networks 15 (2002) 479–493
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
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
Role of Prefrontal cortex in Cognition
• Working memory• Behavioral inhibition• Attentional processing• Future planning
L.A. Briand et al. / Progress in Neurobiology; 83 (2007)
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)
Principles of Neural science, Kandle and Shwartz,4th edition
Neuromodulatory systems projecting to PFC
• Cholinergic system• Serotonergic system• Adrenergic system• Dopaminergic system• Histaminergic system• Volume transmission• Neuropeptides
Basal Forebrain and brainstem cholinergic projections
Newman et al; June 2012; Frontiers in Behavioral Neuroscience;
Newman et al; June 2012; Frontiers in Behavioral Neuroscience;
Cholinergic receptors
• Muscarinic receptors M1 & M2M1 subtypes: m1, m3, m5 (Layer I, II)M2 subtypes: m2, m4 (Layer III, V )• Nicotinic receptorsα subunits (α2-10 )β subunits (β 2-4 )
Principles of Neural science, Kandle and Shwartz,4th edition
Experimental evidences of modulation of cognitive functions
• Cholinotoxins: 192 IgG saporin• Microdialysis studies• Electrophysiological studies• Pharmacological studies
Cued appetitive response task
ME Hasselmo and M Sarter, NeuropsychopharmacologyREVIEWS(2011) 36, 52–73
• cholinergic system is required specifically for the detection of cues.
• It increases the signal to noise ratio (Metherate & Ashe 1991)
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
The Gestalt law of Visual Grouping and Acetylcholine
• 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.
Noradrenergic modulation of prefrontal cholinergic function
Source: Locus cereoleusReceptors: α 1 & α 2
α 1 agonists increases Ach release
α 2 agonists decreases Ach releaseAtomoxetine : NE reuptake inhibitor enhances Ach
releaseEffect on basal forebrain: Depolarise cholinergic
neurons
L.A. Briand et al. / Progress in Neurobiology; 83 (2007)
Serotonergic modulation of prefrontal function
Source : Dorsal raphe nucleusReceptors: 5-HT (1-7) subtypes5-HT 2 Agonists increase Ach release5-HT 3 Agonists decrease Ach release
L.A. Briand et al. / Progress in Neurobiology; 83 (2007)
Dopaminergic modulation of prefrontal function
Source: Ventral tegmental mesocortical neuronsReceptors: D1,D2,D3
D1 Agonists increase Ach releaseD2 Agonists has no effectD3 Agonists decreases Ach release
L.A. Briand et al. / Progress in Neurobiology; 83 (2007)
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