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I need to call this post #1 in the ‘you don’t really want to read this post’ series (although you are certainly welcome to!). I am ‘on the hunt’ for information about dopamine and reward, and am filing information as I go along on my blog for safekeeping.
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“Dopamine may therefore be a neural substrate for novelty or reward expectation rather than reward itself.”
Dissociation of dopamine release in the nucleus accumbens from intracranial self-stimulation
Paul A. Garris, Michaux Kilpatrick, Melissa A. Bunin, Darren Michael, Q. David Walker & R. Mark Wightman
Nature 398, 67-69 (4 March 1999) | doi:10.1038/18019; Received 26 August 1998; Accepted 29 December 1998
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“Behavioural significance of the regional variation in the catecholaminergic control of long-term potentiation
The consolidation of LTP [In neuroscience, long-term potentiation (LTP) is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength. As memories are thought to be encoded by modification of synaptic strength, LTP is widely considered one of the major cellular mechanisms that underlies learning and memory.] is powerfully regulated by NA in both the dentate gyrus (e.g., present results) and CA3, at least for the mossy fibre synapses, (22,24) yet DA plays this role in CA1. What is the behavioural significance of this dissociation?
While it is difficult to completely characterize their repertoire of responding in behaving animals, it is noteworthy that neurons in the locus coeruleus [a nucleus in the brain stem involved with physiological responses to stress and panic], source of the NA [sodium] innervation to the hippocampus, are phasically activated by both noxious and nonnoxious stimuli.(4) They are also tonically inhibited during slow-wave sleep, but show marked activation just prior to waking. (3) For these and other reasons, the locus coeruleus has often been described as participating in behavioural arousal as well as orienting responses and attention, (2–4) through its divergent modulation of multiple brain regions.
Dopaminergic neurons in the ventral midbrain , on the other hand, are typically activated during the expectation or receipt of positive reward.(27,39) [Midbrain, also called the mesencephalon — During development, the mesencephalon forms from the middle of three vesicles that arise from the neural tube to generate the brain. The mesencephalon is considered part of the brain stem. Its substantia nigra is closely associated with motor system pathways of the basal ganglia. The human mesencephalon is archipallian in origin, meaning its general architecture is shared with the most ancient of vertebrates. Dopamine produced in the substantia nigra plays a role in motivation and habituation of species from humans to the most elementary animals such as insects.]
These differences in neural responses to behavioural stimuli suggest that consolidation of LTP, and to some extent its induction, may show regional variations in its sensitivity to the behavioural state of the animals.
It has been suggested that, during exploration and initial learning, there is selective activation of the entorhinal–dentate–CA3 pathway, during which selective synaptic modifications may occur. Modification of these pathways would be turned off during later behaviourally quiet periods or slow-wave sleep. (13) This fits well with the noradrenergic control of dentate gyrus and CA3 LTP, since these periods of learning correspond well with the behavioural situations when locus coeruleus neurons are active.
Conversely, it has been observed that, during behaviourally quiet periods, slow-wave sleep and consummatory behaviours, there are sporadic bursts of activity in CA3 that phasically drive CA1 neurons (sharp waves),(12) and this may reflect the read-out of CA3-localized memory back through CA1 to the cortex for consolidation purposes. (13,31)
During periods of reward consummation, therefore, there may be a conjunction of dopaminergic activity and synaptic activity in CA1 and perhaps other limbic cortical areas, promoting the induction and consolidation of plasticity in these brain areas. It is noteworthy, however, that endogenous catecholamines can influence persistence of LTP in hippocampal slices, which are cut off from the influences of afferent activity originating extrinsically to the hippocampus. Thus, endogenous catecholamines can affect LTP independently of behavioural state. This could simply reflect there being a constitutive release of catecholamines in slices, or that catecholaminergic fibres are being directly stimulated during the experiments. Another more intriguing possibility, however, is that the catecholamine release is locally controlled by glutamate released at activated synapses. There is evidence that glutamate can facilitate catecholamine release from synaptosomes via presynaptic glutamate receptors on catecholaminergic terminals, (46) and there may be sufficient extrasynaptic spillover of glutamate during high-frequency stimulation to activate these receptors in situ. (7) Alternatively, a mobile trans-synaptic messenger such as nitric oxide could serve a similar function. The finding that tetanization-induced cyclic-AMP accumulation in CA1 is blocked by both SCH-23390 and an NMDA receptor antagonist supports this latter possibility. (16) If either of these scenarios were the case, then endogenous high-frequency activity in the hippocampus may have the capacity to be selfreinforcing, regardless of the activity state of the catecholamine cell bodies. This would provide a means for promoting the local consolidation of LTP, specific to the region of the activated synapses, without requiring a flood of catecholamine release throughout widespread regions of the brain that would be initiated by ventral tegmental area or locus coeruleus activity.
CONCLUSIONS
Our results have demonstrated a double dissociation of the catecholaminergic control of persistence of LTP between area CA1 and the dentate gyrus of the hippocampus. NA plays a privileged role promoting the late phase of LTP in the dentate gyrus, while DA fulfils that role in area CA1. Our findings are most complete for the in vitro preparation, and are indicative that the same functions are fulfilled by DA in vivo. Recent data have confirmed that NA plays a vital role in persistence of LTP in the dentate gyrus in vivo.40 Overall, these data suggest that LTP in these brain areas may be differentially consolidated according to the animal’s behavioural state.”
J. L. SWANSON-PARK, C. M. COUSSENS, S. E. MASON-PARKER, C. R. RAYMOND, E. L. HARGREAVES, M. DRAGUNOW, A. S. COHEN and W. C. ABRAHAM — New Zealand – [bold type is mine — click on title for full article including references noted]
Neuroscience Vol. 92, No. 2, pp. 485–497, 1999 Copyright
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ABSTRACT: “What are the genetic and neural components that support adaptive learning from positive and negative outcomes?
Here, we show with genetic analyses that three independent dopaminergic mechanisms contribute to reward and avoidance learning in humans.
A polymorphism in the DARPP-32 gene, associated with striatal dopamine function, predicted relatively better probabilistic reward learning.
Conversely, the C957T polymorphism of the DRD2 gene, associated with striatal D2 receptor function, predicted the degree to which participants learned to avoid choices that had been probabilistically associated with negative outcomes.
The Val/Met polymorphism of the COMT gene, associated with prefrontal cortical dopamine function, predicted participants’ ability to rapidly adapt behavior on a trial-to-trial basis.
These findings support a neurocomputational dissociation between striatal and prefrontal dopaminergic mechanisms in reinforcement learning. Computational maximum likelihood analyses reveal independent gene effects on three reinforcement learning parameters that can explain the observed dissociations.”
Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning
Michael J. Frank, Ahmed A. Moustafa, Heather M. Haughey, Tim Curran, and Kent E. Hutchison
PNAS, October 9, 2007, Vol. 104, No. 41, pages 11311-16316
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Stop the Storm 