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LeDoux and the amygdala

Posted by zeugma on January 1, 2006, at 13:50:36

In reply to Re: what is Fos-Immunoreactivity?, posted by linkadge on December 30, 2005, at 20:31:41

Comments about LeDoux' book "Synaptic Self":

LeDoux' book draws attention to two main concepts or principles in neuroscience:

1)Hebb's "neurons that fire together, wire together" model of learning at the synaptic level;

2) Kandel and Spencer's injunction to study neuronal connections at the levels of the simplest systems possible. This made discovery of long-term potentiation possible, which had been predicted by Hebb many years before.

Since LeDoux is not very theoretically-minded, he is not able, in my opionion, to give an account of the implications of 1). For instance (and this is what I was primarily interested in as I read the bok), he points out that neuromodulators such as serotonin, acytylcholine, etc., significantly alter the synaptic connections between neurons, and notes that this is crucial in memory formation, but does not give this a proper emphasis in terms of its importance in acquisition of generally adaptive or maladaptive behaviors. So he devotes a great deal of time to explaining how long-term potentiation processes influence fear conditioning in rodents, but has little to say about how this might relate to human anxiety and mood disorders.This, however, is the abstract of a more recent work which focuses on the amygdala and its role in anxiety disorders:

It is currently believed that the acquisition of classically conditioned fear involves potentiation of conditioned thalamic inputs in the lateral amygdala (LA). In turn, LA cells would excite more neurons in the central nucleus (CE) that, via their projections to the brain stem and hypothalamus, evoke fear responses. However, LA neurons do not directly contact brain stem-projecting CE neurons. This is problematic because CE projections to the periaqueductal gray and pontine reticular formation are believed to generate conditioned freezing and fear-potentiated startle, respectively. Moreover, like LA, CE may receive direct thalamic inputs communicating information about the conditioned and unconditioned stimuli. Finally, recent evidence suggests that the CE itself may be a critical site of plasticity. This review attempts to reconcile the current model with these observations. We suggest that potentiated LA outputs disinhibit CE projection neurons via GABAergic intercalated neurons, thereby permitting associative plasticity in CE. Thus plasticity in both LA and CE would be necessary for acquisition of conditioned fear. This revised model also accounts for inhibition of conditioned fear after extinction.

http://jn.physiology.org/cgi/content/full/92/1/1

1: Neuroimage. 2004 Oct;23(2):483-99.

Since LeDoux implies, but does not expand upon, hints that the amygdala is importance in reward- and well as fear- driven processes, the following article is relevant:

For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion.

Ochsner KN, Ray RD, Cooper JC, Robertson ER, Chopra S, Gabrieli JD, Gross JJ.

Department of Psychology, Columbia University, 369 Schermerhorn Hall, New York, NY 10027, USA. ochsner@psych.columbia.edu

Functional neuroimaging studies examining the neural bases of the cognitive control of emotion have found increased prefrontal and decreased amygdala activation for the reduction or down-regulation of negative emotion. It is unknown, however, (1) whether the same neural systems underlie the enhancement or up-regulation of emotion, and (2) whether altering the nature of the regulatory strategy alters the neural systems mediating the regulation. To address these questions using functional magnetic resonance imaging (fMRI), participants up- and down-regulated negative emotion either by focusing internally on the self-relevance of aversive scenes or by focusing externally on alternative meanings for pictured actions and their situational contexts. Results indicated (1a) that both up- and down-regulating negative emotion recruited prefrontal and anterior cingulate regions implicated in cognitive control, (1b) that amygdala activation was modulated up or down in accord with the regulatory goal, and (1c) that up-regulation uniquely recruited regions of left rostromedial PFC implicated in the retrieval of emotion knowledge, whereas down-regulation uniquely recruited regions of right lateral and orbital PFC implicated in behavioral inhibition. Results also indicated that (2) self-focused regulation recruited medial prefrontal regions implicated in internally focused processing, whereas situation-focused regulation recruited lateral prefrontal regions implicated in externally focused processing. These data suggest that both common and distinct neural systems support various forms of reappraisal and that which particular prefrontal systems modulate the amygdala in different ways depends on the regulatory goal and strategy employed.

A proposed mechanism for how the amygdala could influence reward-driven processes is given here:

J Comp Neurol. 2005 Aug 29;489(3):349-71. Related Articles, Links


Afferent connections of the amygdalopiriform transition area in the rat.

Santiago AC, Shammah-Lagnado SJ.

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo SP 05508-900, Brazil.

The amygdalopiriform transition area (APir) is often considered part of the lateral entorhinal cortex (Entl). However, in contrast to Entl, APir densely innervates the central extended amygdala (EAc) and does not project to the dentate gyrus. In order to gain a more comprehensive understanding of these territories, the afferent connections of APir were examined in the rat with retrograde (cholera toxin B subunit or FluoroGold) and anterograde tracers (Phaseolus vulgaris leucoagglutinin) and compared to those of the neighboring Entl. The results suggest that APir and Entl are interconnected and receive topographically organized hippocampal projections. Both are targeted by the olfactory bulb, the piriform, posterior agranular insular and perirhinal cortices, the ventral tegmental area, dorsal raphe nucleus, and locus coeruleus. Most importantly, the data reveal that APir and Entl also have specific inputs and should be viewed as separate anatomical entities. The APir receives robust projections from structures affiliated with the EAc, including the anterior basomedial and posterior basolateral amygdaloid nuclei, the gustatory thalamic region, parasubthalamic nucleus, and parabrachial area. The Entl is a major recipient for amygdaloid projections from the medial part of the lateral nucleus and the caudomedial part of the basolateral nucleus. Moreover, the medial septum, subicular complex, nucleus reuniens, supramammillary region, and nucleus incertus, which are associated with the hippocampal system, preferentially innervate the Entl. These data underscore that APir processes olfactory and gustatory information and is tightly linked to EAc operations, suggesting that it may play a role in reward mechanisms, particularly in hedonic aspects of feeding.

-z



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