Gamma oscillations in the basolateral amygdala: localization, microcircuitry, and behavioral correlates.

The lateral (LA) and basolateral (BL) nuclei of the amygdala regulate emotional behaviors. Despite their dissimilar extrinsic connectivity, they are often combined, perhaps because their cellular composition is similar to that of the cerebral cortex, including excitatory principal cells reciprocally connected with fast-spiking interneurons (FSIs). In the cortex, this microcircuitry produces gamma oscillations that support information processing and behavior. We tested whether this was similarly the case in the rat (males) LA and BL using extracellular recordings, biophysical modeling, and behavioral conditioning. During periods of environmental assessment, both nuclei exhibited gamma oscillations that stopped upon initiation of active behaviors. Yet, BL exhibited more robust spontaneous gamma oscillations than LA. The greater propensity of BL to generate gamma resulted from several microcircuit differences, especially the proportion of FSIs and their interconnections with principal cells. Furthermore, gamma in BL but not LA regulated the efficacy of excitatory synaptic transmission between connected neurons. Together, these results suggest fundamental differences in how LA and BL operate. Most likely, gamma in LA is externally driven whereas in BL, it can also arise spontaneously to support ruminative processing and the evaluation of complex situations.SIGNIFICANCE STATEMENT:The basolateral amygdala (BLA) participates in the production and regulation of emotional behaviors. It is thought to perform this using feedforward circuits that enhance stimuli that gain emotional significance and directs them to valence-appropriate downstream effectors. This perspective overlooks the fact that its microcircuitry is recurrent and potentially capable of generating oscillations in the gamma band (50-80 Hz), which synchronize spiking activity and modulate communication between neurons. This study found that BLA gamma supports both these processes, is associated with periods of action selection and environmental assessment irrespective of valence, and differs between BLA subnuclei in a manner consistent with their heretofore unknown microcircuit differences. Thus, it provides new mechanisms for BLA to support emotional behaviors.

Different Multidimensional Representations across the Amygdalo-Prefrontal Network during an Approach-Avoidance Task.

The prelimbic (PL) area and basolateral amygdala (lateral [LA] and basolateral [BL] nuclei) have closely related functions and similar extrinsic connectivity. Reasoning that the computational advantage of such redundancy should be reflected in differences in how these structures represent information, we compared the coding properties of PL and amygdala neurons during a task that requires rats to produce different conditioned defensive or appetitive behaviors. Rather than unambiguous regional differences in the identities of the variables encoded, we found gradients in how the same variables are represented. Whereas PL and BL neurons represented many different parameters through minor variations in firing rates, LA cells coded fewer task features with stronger changes in activity. At the population level, whereas valence could be easily distinguished from amygdala activity, PL neurons could distinguish both valence and trial identity as well as or better than amygdala neurons. Thus, PL has greater representational capacity.

Embracing Complexity in Defensive Networks.

The neural basis of defensive behaviors continues to attract much interest, not only because they are important for survival but also because their dysregulation may be at the origin of anxiety disorders. Recently, a dominant approach in the field has been the optogenetic manipulation of specific circuits or cell types within these circuits to dissect their role in different defensive behaviors. While the usefulness of optogenetics is unquestionable, we argue that this method, as currently applied, fosters an atomistic conceptualization of defensive behaviors, which hinders progress in understanding the integrated responses of nervous systems to threats. Instead, we advocate for a holistic approach to the problem, including observational study of natural behaviors and their neuronal correlates at multiple sites, coupled to the use of optogenetics, not to globally turn on or off neurons of interest, but to manipulate specific activity patterns hypothesized to regulate defensive behaviors.

Basolateral amygdala neurons are activated during threat expectation.

Fear conditioning studies have led to the view that the amygdala contains neurons that signal threat and in turn elicit defensive behaviors through their brain stem and hypothalamic targets. In agreement with this model, a prior unit-recording study in rats performing a seminaturalistic foraging task revealed that many lateral amygdala (LA) neurons are predator responsive. In contrast, our previous study emphasized that most basolateral (BL) amygdala neurons are inhibited at proximity of the predator. However, the two studies used different methods to analyze unit activity, complicating comparisons between them. By applying the same method to the sample of BL neurons we recorded previously, the present study revealed that most principal cells are inhibited by the predator and only 4.5% are activated. Moreover, two-thirds of these cells were also activated by nonthreatening stimuli. In fact, fitting unit activity with a generalized linear model revealed that the only task variables associated with a prevalent positive modulation of BL activity were expectation of the predator's presence and whether the prior trial had been a failure or success. At odds with the threat-coding model of the amygdala, actual confrontation with the predator was usually associated with a widespread inhibition of principal BL neurons. NEW & NOTEWORTHY The basolateral amygdala (BL) is thought to contain neurons that signal threat, in turn eliciting defensive behaviors. In contrast, the present study reports that very few principal BL cells are responsive to threats and that most of them are also activated by nonthreatening stimuli. Yet, expectation of the threat's presence was associated with a prevalent positive modulation of BL activity; actual confrontation with the threat was associated with a widespread inhibition.

Multi-dimensional Coding by Basolateral Amygdala Neurons.

Conditioned appetitive and aversive responses (CRs) are thought to result from the activation of specific subsets of valence-coding basolateral amygdala (BLA) neurons. Under this model, the responses of BLA cells to conditioned stimuli (CSs) and the activity that drives CRs are closely related. We tested the strength of this correlation using a task where rats could emit different CRs in response to the same CSs. At odds with this model, the CS responses and CR-related activity of individual BLA cells were separable. Moreover, while the incidence of valence-coding cells did not exceed chance, at the population level there was similarity between valence coding for CSs and CRs. In fact, both lateral and basolateral neurons concurrently encoded multiple task features and behaviors. Thus, conditioned emotional behaviors may not depend on the recruitment of single cells that explicitly encode individual task variables but from multiplexed representations distributed across the BLA.