Functional Internal Complexity of Amygdala: Focus on Gene Activity Mapping After Behavioral Training and Drugs of Abuse

The amygdala is a heterogeneous brain structure implicated in processing of emotions and storing the emotional aspects of memories. Gene activity markers such as c-Fos have been shown to reflect both neuronal activation and neuronal plasticity. Herein, we analyze the expression patterns of gene activity markers in the amygdala in response to either behavioral training or treatment with drugs of abuse and then we confront the results with data on other approaches to internal complexity of the amygdala. c-Fos has been the most often studied in the amygdala, showing specific expression patterns in response to various treatments, most probably reflecting functional specializations among amygdala subdivisions. In the basolateral amygdala, c-Fos expression appears to be consistent with the proposed role of this nucleus in a plasticity of the current stimulus-value associations. Within the medial part of the central amygdala, c-Fos correlates with acquisition of alimentary/gustatory behaviors. On the other hand, in the lateral subdivision of the central amygdala, c-Fos expression relates to attention and vigilance. In the medial amygdala, c-Fos appears to be evoked by emotional novelty of the experimental situation. The data on the other major subdivisions of the amygdala are scarce. In conclusion, the studies on the gene activity markers, confronted with other approaches involving neuroanatomy, physiology, and the lesion method, have revealed novel aspects of the amygdala, especially pointing to functional heterogeneity of this brain region that does not fit very well into contemporarily active debate on serial versus parallel information processing within the amygdala.

Ewelina Knapska, Kasia Radwanska, Tomasz Werka, and Leszek Kaczmarek.
Functional Internal Complexity of Amygdala: Focus on Gene Activity Mapping After Behavioral Training and Drugs of Abuse.
Physiol. Rev. 87: 1113-1173, 2007. doi:10.1152/physrev.00037.2006.

http://physrev.physiology.org/cgi/content/abstract/87/4/1113

Lesions of the Basal Amygdala Block Expression of Conditioned Fear But Not Extinction

Although the role of the amygdala in acquisition of conditioned fear is well established, there is debate concerning the intra-amygdala circuits involved. The lateral nucleus of the amygdala (LA) is thought to be an essential site of plasticity in fear conditioning. The LA has both direct and indirect [via the basal nuclei; basal amygdala (BA)] projections to the central nucleus (Ce) of the amygdala, an essential output for fear behaviors. Lesions of the LA or Ce prevent acquisition of conditioned freezing to a conditioned stimulus, but BA lesions do not, suggesting that the BA is not normally involved in fear conditioning. If true, posttraining BA lesions should also have no effect. Replicating previous studies, we found that rats given electrolytic BA lesions before training acquired conditioned fear normally. They also showed normal long-term retention and extinction of conditioned fear. Unexpectedly, BA lesions made after training completely blocked expression of conditioned fear. Despite this deficit, lesioned rats were able to learn a new tone-shock association. Thus, although the LA-Ce system is sufficient for fear acquisition in the absence of the BA, it is not sufficient when the BA is present, suggesting that the BA is an important site of plasticity in fear conditioning. The pattern of lesion deficits we observed (after but not before training) might be explained by homeostatic mechanisms that balance plasticity over multiple inputs, regulating the influence of the BA and LA onto Ce output neurons.



Figure 5. Model to account for deficits with posttraining, but not pretraining, lesions. We suggest that homeostatic mechanisms that balance plasticity over multiple inputs could regulate the influence of the BA, LA, and MGm onto CeM neurons. 1, The CeM receives inputs from the MGm, BA, and LA via ITC cells (dashed line). 2, After fear conditioning, BA inputs gain a large proportion of the total plasticity, inhibiting the development of plasticity in neighboring inputs. 3, Posttraining lesions of the BA remove this plasticity, leaving the system subthreshold for producing a fear response. 4, With pretraining removal of the BA, however, increased plasticity in the LA and MGm supports fear learning. For simplicity, projections from the MGm to the LA and from the LA to the BA are not shown.

David Anglada-Figueroa, and Gregory J. Quirk
Lesions of the Basal Amygdala Block Expression of Conditioned Fear But Not Extinction
J. Neurosci. 25: 9680-9685; doi:10.1523/JNEUROSCI.2600-05.2005

http://www.jneurosci.org/cgi/content/full/25/42/9680

Cortical Connections of the Insular and Adjacent Parieto-temporal Fields in the Cat

We present a comprehensive analysis of the cortical connections of the insular and adjacent cortical areas in the domestic cat by using microinjections of wheat-germ agglutinin conjugated to horseradish peroxidase. We examined the identity and extent of the cortical fields connected to each area, the relative anatomical weights of the various connections, their laminar origin, and their paths across the cerebral commissures. Our main finding is that despite their relatively small size and close apposition, the connections of the insular and adjacent areas are far more widespread and more specific to each area than previously realized, suggesting that each area is involved in disparate aspects of cortical integration. The granular insular area is linked to a constellation of somatosensory, motor, premotor and prefrontal districts. The dysgranular insular area is chiefly associated with lateral prefrontal and premotor, lateral somatosensory and perirhinal cortices. The dorsal agranular insular area is connected with limbic neocortical fields, while the ventral agranular insular area is associated with an array of olfactory allocortical fields. The anterior sylvian area is associated with visual, auditory and multimodal areas, with the dorsolateral prefrontal cortex, and with perirhinal area 36. The parainsular area is linked to non-tonotopic auditory and ventromedial frontal areas. Trajectories followed by the callosal axons of each of the investigated areas are extremely divergent. As a whole, the picture of the insular region that emerges from this and a parallel study (Clascá et al., J Comp Neurol 384:456–482, 1997) is that of an extreme heterogeneity, both in terms of histological architecture and neural connections. Comparison with earlier published reports on primates suggests that most, but not all, of the areas we investigated in cats may have an direct counterpart within the insula of Old World monkeys.



Figure 1



Figure 17. Summary of cortical and thalamic relationships of the areas under study. Each panel represents the connections of an area on standard medial and lateral views of the hemisphere. Outlined letters identify the area of interest. Thicker lines and bold case highlight heavier connections, while thin or dashed lines indicate less numerous connections. Thalamic input is represented by the ellipsoids and arrow at the bottom of each panel. Connections of (A) GI, (B) DI, (C) AId, (D) AIv, (E) Pi, (F) AS. Abbreviations for thalamic nuclei (n): CeM, centralis medialis n.; LM, lateralis medialis n.; M(D), mediodorsal nucleus; MGm, medial geniculate n., medial division; MGvl, medial geniculate n., ventrolateral subnucleus; Pf, parafascicular n.; PoM, posterior thalamic n., medial division; Re, reuniens n.; Rh, rhomboid n.; VL, ventrolateral n.; VM, ventromedial n.; VPi, ventralis posteroinferior n.; VPmP, ventralis posteromedialis n., peripheral subnucleus. For other abbreviations see Table 1.

Francisco Clascá , Alfonso Llamas , and Fernando Reinoso-Suárez
Cortical Connections of the Insular and Adjacent Parieto-temporal Fields in the Cat.
Cereb. Cortex 10: 371-399.

http://cercor.oxfordjournals.org/cgi/content/full/10/4/371

Superior temporal gyrus and insula provide response and outcome-dependent information during assessment and action selection in a decision-making ...

Decision-making is a complex process that comprises the assessment of a situation, the selection of an action, and the evaluation of an outcome. Distinct neural systems may contribute differentially during various stages within a decision-making situation. This study investigated whether neural activation during assessment or action selection is critically dependent on previous outcomes or actions. Twelve healthy, right-handed subjects (6 females) played a Rock Paper Scissors (RPS) computer game during functional magnetic resonance imaging. Bilateral insula and medial prefrontal cortex (including the anterior cingulate) were specifically engaged during the assessment and action selection stages of decision-making, whereas bilateral superior frontal gyrus and right inferior parietal lobule activated more during the outcome. Two regions of activation within the bilateral superior temporal gyrus activated only when the previous outcome was a win. Moreover, right insula and superior temporal gyrus were active more when the subject switched responses relative to staying with the same choice made on the previous trial. These findings support the hypothesis that distinct neural systems underlie different stages of the decision-making process. Furthermore, the superior temporal gyrus may play an important role in integrating previous actions and successful outcomes into one's decision-making strategy.

Paulus MP, Feinstein JS, Leland D, Simmons AN.
Superior temporal gyrus and insula provide response and outcome-dependent information during assessment and action selection in a decision-making situation.
Neuroimage. 2005 Apr 1;25(2):607-15.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=15784440

Interactions between the Orbitofrontal Cortex and the Hippocampal Memory System during the Storage of Long-Term Memory

It has been proposed that long-term declarative memories are ultimately stored through interactions between the hippocampal memory system and the neocortical association areas that initially processed the to-be-stored information. One association neocortex, the orbitofrontal cortex (OFC) is strongly and reciprocally connected with the hippocampal memory system and plays an important role in odor recognition memory in rats. We will report data from two studies: one that examined the firing of neurons in a task dependent on the parahippocampal region (PHR; including the perirhinal, postrhinal, and entrorhinal cortices), and one examined the firing of OFC neurons performing a task that is presumably dependent on the hippocampus. In the first study, we examined the role of OFC neurons in the continuous odor-guided nonmatching to sample task. While the firing of neurons in the PHR and OFC are similar in this task, there are several notable differences that are consistent with the idea that OFC is a high-order association cortex which interacts extensively with the PHR to store declarative memories. In the second study, we characterized the firing patterns of neurons in the OFC rats performing a passive, 8-odor-sequence memory task. Most interesting were neurons that fired selectively in anticipation of specific odors. We found that hippocampal lesions abolished the anticipatory firing in OFC, suggesting that these anticipatory responses (memory) were in fact dependent on the hippocampus, further supporting the view that the OFC interacts with the hippocampal memory system to store long-term, declarative memories.

SETH J. RAMUS, JENA B DAVIS, RACHEL J DONAHUE, CLAIRE B DISCENZA, and ALISSA A. WAITE.
Interactions between the Orbitofrontal Cortex and the Hippocampal Memory System during the Storage of Long-Term Memory.
Ann NY Acad Sci 2007 1121: 216-231.

http://www.annalsnyas.org/cgi/content/abstract/1121/1/216

Neural coding of reward magnitude in the orbitofrontal cortex of the rat during a five-odor olfactory discrimination task

The orbitofrontal cortex (OBFc) has been suggested to code the motivational value of environmental stimuli and to use this information for the flexible guidance of goal-directed behavior. To examine whether information regarding reward prediction is quantitatively represented in the rat OBFc, neural activity was recorded during an olfactory discrimination "go"/"no-go" task in which five different odor stimuli were predictive for various amounts of reward or an aversive reinforcer. Neural correlates related to both actual and expected reward magnitude were observed. Responses related to reward expectation occurred during the execution of the behavioral response toward the reward site and within a waiting period prior to reinforcement delivery. About one-half of these neurons demonstrated differential firing toward the different reward sizes. These data provide new and strong evidence that reward expectancy, regardless of reward magnitude, is coded by neurons of the rat OBFc, and are indicative for representation of quantitative information concerning expected reward. Moreover, neural correlates of reward expectancy appear to be distributed across both motor and nonmotor phases of the task.

van Duuren, Esther, Escamez, Francisco A. Nieto, Joosten, Ruud N.J.M.A., Visser, Rein, Mulder, Antonius B., Pennartz, Cyriel M.A.
Neural coding of reward magnitude in the orbitofrontal cortex of the rat during a five-odor olfactory discrimination task.
Learn. Mem. 2007 14: 446-456.

http://www.learnmem.org/cgi/content/abstract/14/6/446

Associative Encoding in Anterior Piriform Cortex versus Orbitofrontal Cortex during Odor Discrimination and Reversal Learning

Recent proposals have conceptualized piriform cortex as an association cortex, capable of integrating incoming olfactory information with descending input from higher order associative regions such as orbitofrontal cortex (OFC). If true, encoding in piriform cortex should reflect associative features prominent in these areas during associative learning involving olfactory cues. To test this hypothesis, we recorded from neurons in OFC and anatomically related parts of the anterior piriform cortex (APC) in rats, learning and reversing novel odor discriminations. Findings in OFC were similar to what we have reported previously, with nearly all the cue-selective neurons exhibiting substantial plasticity during learning and reversal. Also, many of the cue-selective neurons were originally responsive in anticipation of the outcomes early in learning, thereby providing a single-unit representation of the cue-outcome associations. Some of these features were also evident in firing activity in APC, including some plasticity across learning and reversal. However, APC neurons failed to reverse cue selectivity when the associated outcome was changed, and the cue-selective population did not include neurons that were active prior to outcome delivery. Thus, although representations in APC are substantially more associative than expected in a purely sensory region, they do appear to be somewhat more constrained by the sensory features of the odor cues than representations in downstream areas of OFC.

Matthew R. Roesch , Thomas A. Stalnaker , and Geoffrey Schoenbaum.
Associative Encoding in Anterior Piriform Cortex versus Orbitofrontal Cortex during Odor Discrimination and Reversal Learning.
Cerebral Cortex Advance Access published on March 1, 2007, DOI 10.1093/cercor/bhk009. Cereb. Cortex 17: 643-652.

http://cercor.oxfordjournals.org/cgi/content/abstract/17/3/643