Optogenetics Discovers Brain Anxiety Circuit

AmygdCingGyrusThe state of heightened apprehension and high arousal in the absence of immediate threat—commonly labeled as acute stress or anxiety—can be a severely debilitating condition. Over 28% of the population suffers from anxiety disorders that contribute to the development of major depressive disorder and substance abuse. Of all the structures of the limbic system, the seat of emotion processing, the amygdala plays a key role in anxiety, although by what exact mechanism still remains unclear. Newly published research carried out by a group of neuroscientists at Stanford University using the novel technique of optogenetics with two-photon microscopy has permitted a much closer exploration of the neural circuits underlying anxiety than ever before. The optogenetics approach facilitates the identification not only of cell types but also the specific connections between cells. The researchers noticed that timed optogenetic stimulation of the basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA) produced a significant, acute, and reversible anxiety-reducing effect. Conversely, selective optogenetic inhibition of the same projection resulted in increased anxiety-related behaviors. These results indicate that specific BLA–CeA projections are the critical circuit elements for acute anxiety control in the brain. The results were published in the March 17 issue of the scientific journal Nature.

A Closer Look at the Amygdala’s BLA and CeA Regions

BasolateralAmygdalaThe amygdalae (amygdaloid nucleus) are two identical almond-shaped brain structures located in each temporal lobe. Each amygdala receives input from the olfactory system, as well as from visceral structures. The amygdala in humans has been confirmed by functional MRI imaging to be the area of the brain that is best correlated with emotional reactions and plays a key role in the brain’s integration of emotional meaning with perception and experience. The emotional aspect of the response of the individual is passed on to the frontal cortex, where “decisions” are made regarding possible responses. In this way, the response of the individual can take into account the emotional aspect of the situation.

Additionally, the amygdala coordinates the actions of the autonomic and endocrine systems and prompts release of adrenaline and other excitatory hormones into the bloodstream. The amygdala is involved in producing and responding to nonverbal signs of anger, avoidance, defensiveness, and fear. The amygdala has been implicated in emotional dysregulation, aggressive behavior, and psychiatric illnesses such as depression. It has also been shown to play an important role in the formation of emotional memory and in temporal lobe epilepsy.

The basolateral amygdala, one of the two structures studied in the recent Stanford research, receives extensive projections from areas of the brain cortex that are specialized for recognizing objects such as faces in central vision. Extensive intrinsic connections within the amygdala
promote further coordination of sensory information.

Biological effects initiated by amygdala include increases or decreases in arterial pressure and heart rate, gastrointestinal motility and secretion, evacuation, pupillary dilation, piloerection, and secretion of various anterior pituitary hormones, especially the gonadotropins and
adrenocorticotropic hormone, which are key agents in the stress reaction. Interestingly, amygdala stimulation can also cause several types of involuntary movement, such as raising the head or bending the body, circling movements, occasionally rhythmical movements, and movements
associated with taste and eating, such as licking, chewing, and swallowing.

LimbicSystemGeographyThe findings also show the involvement of the amygdala’s CeA region in mediating threat-related anxiety and acute fear-related behavioral and hormonal responses. Earlier studies had shown that stimulation of this same area reduces snake fear and pituitary-adrenal activity and that CeA lesions resulted in decreased expression of threat-induced freezing. Additionally, the CeA region of the amygdala was reported as being significantly involved in the consolidation of contextual fear memory, i.e., what permits us to remember so vividly and persistently objects or situations that have caused fear in us in the past.