Fear and Loathing in the Amygdala

Our understanding of fear responses in mammals improved last week, thanks to 2 rodent studies published in the latest issue of Nature (see here and here). In a combined analysis of the work, Australian scientists Pankaj Sah and Frederick Westbrook provide an overview of the circuitry now implicated in fear conditioning. Fear conditioning is a process whereby a normally innocuous stimulus (eg, a flashing light) is paired with a noxious, fear-producing stimulus (eg, an electric shock) to produce a fear response after exposure to the innocuous stimulus alone.

The rodent studies indicate that fear conditioning is the result of sensory input from both the innocuous and noxious stimuli into so-called fear neurons of the basolateral portion of the amygdala. (The amygdala is a bilateral, deep-seated collection of neurons within the medial temporal lobes, which can be thought of as the brain's Grand Central Station of emotional reactions.) These fear neurons then activate neurons in another part of the amygdala, the central nucleus, which sends its output to the hippocampus and brainstem to produce a behavioral fear response.

Extinction of the fear response, which occurs after repeated exposure to the innocuous stimulus alone, is the result of activation of intercalated neurons within the amygdala, either directly from the prefrontal cortex or by way of so-called extinction neurons within the basolateral nucleus of the amygdala. These intercalated neurons then inhibit the fear neurons and their input into the central nucleus. Likhtik et al showed that toxic lesions of the intercalated neurons in mice resulted in deficient extinction that correlated inversely with the number of surviving cells.

The renewal of the fear response, which occurs when the innocuous and noxious stimuli are re-paired, is the result of input from the hippocampus, which activates inhibitor neurons in the basolateral amygdala. These inhibitor neurons, in turn, suppress the activity of extinction neurons.

Paj and Westbrook indicate that specific neuronal receptors* within this fear circuitry are likely to become targets for investigational treatments of anxiety and panic disorders in humans.

* The chief transmitter of major inputs into the amygdala is glutamate, and the central nucleus contains inhibitory gamma amino-butyric acid (GABA) receptors, which are potentiated by benzos.

Image of transparent brain from underneath (ventral aspect) showing bilateral amygdalae (red) from Wikipedia.