Keeping synapses clean may hold key to fear-conditioning

2 min read

Discovery could lead to better understanding of debilitating illnesses

As readers of introductory psychology texts know, animals easily learn to fear a harmless stimulus, such as a tone, if that stimulus is paired with a painful one, such as a foot shock. For this fear conditioning to take root in the brain, neurons located in the almond-shaped amygdala must become extraordinarily sensitized to the tone-carrying stimulus — so sensitive that they will continue to fire even in the absence of an auditory stimulus. Yet each neuron in the amygdala is capable of receiving many, even thousands, of inputs.  How are neurons able to exhibit such sensitivity, known as long-term potentiation (LTP), to a single input amid such a plethora of signals? The answer, it appears, is by cleaning up their synapses. For LTP to occur, a presynaptic neuron must release the chemical glutamate in a continuous manner. Normally, glutamate is removed from the synaptic cleft by housekeeping proteins, known as glutamate transporters, in the postsynaptic neuron. Suspecting that this glutamate-removal system might play a role in maintaining input specificity, Vadim Bolshakov, director of McLean Hospital’s Cellular Neurobiology Laboratory, and his colleagues blocked the glutamate transporter in neurons of the amygdala. The cells’ ability to distinguish between inputs was lost. Bolshakov and his colleagues believe that spillover of excess glutamate may be responsible.