Polarized Synaptic Interactions Between Intercalated Neurons of the Amygdala

Abstract

The intercalated (ITC) cell masses are small GABAergic cell clusters interposed between the basolateral (BL) complex and central (CE) nucleus of the amygdala. ITC cells receive excitatory afferents from the BL complex and generate feed-forward inhibition in the CE nucleus. Recently it was shown that ITC cells could gate impulse traffic between the BL complex and CE nucleus in a spatiotemporally differentiated manner. In addition, it was hypothesized that lateromedial inhibitory interactions between different ITC cell clusters played a critical role in this respect. Given the potential importance of such conditional computations, the present study aimed to characterize the connectivity existing among ITC cells. To this end, whole cell recordings of ITC neurons were obtained under visual guidance in coronal slices of the guinea pig amygdala. Electrical stimuli applied in the BL complex primarily elicited excitatory responses when they were applied at the same lateromedial level or more medially than the recorded ITC cells. As the stimulation site was moved laterally, the character of the response shifted toward inhibition. Both bicuculline and non-N-methyl-D-aspartate receptor antagonists abolished this BL-evoked inhibition, suggesting that it was not mediated by BL inhibitory cells projecting to ITC neurons. In keeping with this, local glutamate injections in and around the ITC clusters revealed that the most effective site to inhibit ITC cells were ITC clusters located laterally with respect to the recorded one. The activation of more medial ITC clusters evoked much smaller responses. Thus, connections between ITC clusters tend to run in a lateromedial direction. To identify the source of these directionally polarized synaptic interactions, the morphological features of ITC cells were analyzed by intracellular injection of Neurobiotin. This analysis revealed that the dendritic tree and axonal arbor of ITC cells are asymmetric in the lateromedial plane. In particular, their laterally directed dendrites were longer than the medial ones, whereas their laterally directed axon collaterals were shorter than the medial ones. It is concluded that the morphological asymmetry of ITC cells accounts for the directional polarization of inter-ITC connections. The significance of these findings for the gating of information transfer from the BL complex to the CE nucleus is discussed.

Synergistic Interactions between Cannabinoids and Environmental Stress in the Activation of the Central Amygdala

“…For example, GABAergic cells within intercalated cell masses (ICM), which lie at the anatomical interface of the BLA and CeA, generate feedforward inhibition of CeA neurons in response to BLA activation (Royer et al, 1999(Royer et al, , 2000, and are regulated by extrinsic glutamatergic afferents from the prefrontal cortex and dopaminergic afferents from the ventral midbrain (Bissiere et al, 2003;. Therefore, cannabinoid actions within these regions, which are known to occur (French et al, 1997;Gessa et al, 1998;Auclair et al, 2000;Patel and Hillard, 2003), could modulate CeA activity independently of the BLA, via modulation of ICM neuronal activity.…”

Auditory Fear Circuits in the Amygdala – Insights from Computational Models

“…Also, Amano et al (2011) have shown that the two sub-regions within BA, the lateral part (BL), and the medial part (BM), act in concert to express fear but possess a certain amount of redundancy between themselves. Similarly, there are two different ITC cell clusters and they are thought to contribute differentially to the expression of fear and extinction memories (Royer et al, 2000;Pape and Paré, 2010). The output nucleus Ce also has distinct sub-circuits with different functions in fear learning (Coicci et al, 2010;Haubensak et al, 2010).…”

“…The amygdala intercalated cells (ITC; fig 2) are distributed along the lateral and medial parts of the basolateral amygdaloid complex. The more dorsally located ITC clusters receive glutamatergic excitatory input from LA and BA, while the medial ITC clusters receive GABAergic inhibition from the dorsal ITC clusters and excitation from BA; the medial clusters, in turn, inhibit Ce, the output station in the amygdala (Paré and Smith, 1993a,b;Royer et al, 1999;Royer et al, 2000;Jungling et al, 2008). This strategic location of the medial ITC clusters, between the sensory input (BLA) and fear output (Ce) stations of the amygdala, is thought to be critical for regulating classically conditioned fear responses (Paré et al, 2004).…”

“…Consistent with this, IL stimulation was found to dramatically reduce the responsiveness of Ce neurons to BLA inputs (Quirk et al, 2003). IL axons are known to target ITC cells clusters located medially (McDonald et al, 1996), and there are inhibitory connections between (Royer et al, 2000) as well as within ITC cell clusters (Geracitano et al, 2007). Additionally, three different types of short-term synaptic plasticity have been observed in inter-ITC connections (Geracitano et al, 2007), but the role of such synaptic heterogeneity is not clear.…”

Essential Role for TRPC5 in Amygdala Function and Fear-Related Behavior

“…We also investigated the role of TRPC5 in synaptic transmission at excitatory inputs to intercalated cells (Royer et al, 2000). Residing in a narrow strip of cellular clusters between the BLA complex and the central nucleus of the amygdala (CeA), they receive synaptic inputs from the lateral and basal nuclei and project to the CeA.…”