Wiring and Volume Transmission in Rat Amygdala. Implications for Fear and Anxiety

Abstract

The amygdala plays a key role in anxiety. Information from the environment reaches the amygdaloid basolateral nucleus and after its processing is relayed to the amygdaloid central nucleus where a proper anxiogenic response is implemented. Experimental evidence indicates that in this information transfer a GABAergic interface controls the trafficking of impulses between the two nuclei. Recent work indicates that interneuronal communication can take place by classical synaptic transmission (wiring transmission) and by volume transmission in which the neurotransmitter diffuses and flows through the extracellular space from its site of release and binds to extrasynaptic receptors at various distances from the source. Based on evidence from our laboratory the concept is introduced that neurotransmitters in the amygdala can modulate anxiety involving changes in fear learning and memories by effects on receptor mosaics in the fear circuits through wiring and volume transmission modes of communication.

GABAA ρ receptor mechanisms in the rat amygdala and its role in the modulation of fear and anxiety

“…This suggestion is in line with a diminished open arm exploration observed in rats bred for high anxiety levels (Henninger et al 2000) or treated with anxiogenic compounds (Pellow et al 1985;Davis and Whalen 2001;Pérez de la Mora et al 2008Engin and Treit 2008). Moreover, the effects of the bilateral intra-amygdaloid administration of TPMPA on the exploration of the open arms of the maze do not seem to be secondary to changes in the general activity of the rats as neither the total number of entries into the open + closed arms of the maze, that is a built-in measure of locomotion in the elevated plus-maze (Pellow et al 1985), nor the locomotion in the open-field test was modified.…”

“…Thus, GABA A ρ1 receptors have been detected immunohistochemically in the posterior amygdala (Rosas-Arellano and Miledi, personal communication) and GABA A ρ2 receptors have been found by real-time polymerase chain reaction (RT-PCR) within the BLA and CeA (Esmaeili et al 2009). Furthermore, in line with these results, both the iontophoretic application of GABA to amygdala slices and the electrical stimulation of the medial intercalated paracapsular islands, which are clusters of GABAergic neurons that are interposed between the BLA and CeA and seem to control the flow of nerve impulses between these nuclei (Paré et al 2004;Pérez de la Mora et al 2008, were found to induce within the CeA inhibitory postsynaptic currents that were insensitive to bicuculline and partially blocked by the application of TPMPA (Delaney et al 1999(Delaney et al , 2001.…”

“…Alternatively, a slight loss of the selectivity of TPMPA with blockade of some classical GABA A receptor may have occurred at high doses of the antagonist. Under these conditions, as GABA-GABA receptor interactions between the intercalated paracapsular chain of GABAergic islands seem to be important in modulating the trafficking of impulses within the amygdala and its anxiogenic output (Paré et al 2004;Pérez de la Mora et al 2008, a blockade of GABA A receptors on the GABA neurons responsible to gate the anxiogenic output of the amygdala by TPMPA may lead to the loss of the anxiogenic-like effects observed in our experiments. Finally, in the experiments of Cunha et al (2010), larger doses of TPMPA resulted in anxiolytic effects attributed to the blockade of inhibitory GABA A ρ autoreceptors, and it is conceivable that in our experiments TPMPA at higher doses had acted on postsynaptic and presumably presynaptic GABA A ρ receptors leading to a mixture of anxiogenic and anxiolytic effects.…”

“…It is generally accepted that the amygdala plays an important role in the modulation of fear and anxiety (Davis and Whalen 2001;Everitt et al 2003;Engin and Treit 2008;LeDoux 2000;Millan 2003; Pérez de la Mora et al 2008Mora et al , 2010. Emotionally relevant stimuli from the thalamus and cortex reach the basolateral complex of the amygdala (BLA), and after being processed they are relayed to the amygdaloid central nucleus (CeA) where a proper anxiogenic response is implemented.…”

Intercalated and paracapsular cell islands of the adult rat amygdala: A combined rapid-Golgi, ultrastructural, and immunohistochemical account

“…The amygdala seems to be of paramount importance for the modulation of fear and anxiety (for reviews, see LeDoux, 2000;Everitt et al, 2003;Engin and Treit, 2008;Perez de la Mora et al, 2008). It comprises a number of nuclei, and an array of afferent, efferent, and interconnecting fibers (Nauta, 1962;Swanson and Petrovich, 1998;McDonald, 2003) occupying a large part of the mammalian medial temporal lobe.…”