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
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.
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)
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;
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
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)
Hinweis der Redaktion
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)