December 11, 2018
• Researchers trained mice to fear one type of sound, but expect reward when they heard another
• They performed real time observation of neurons in the basolateral amygdala as animals learned to associate the tones with fear or reward
• They show learning of fear and reward is plastic and can be reversed or remapped
• The research could provide insights into treatments for anxiety and PTSD
PAVLOVIAN CONDITIONING IN THE AMYGDALA
The basolateral amygdala is an area of the brain that encodes valence learning, whether something is attractive to us, or aversive to us.
Positive or negative valences induce typical behaviours. In mice, scientists can associate a painful stimulus such as a foot-shock with a tone or an environment. Meaning mice will freeze when they hear the same tone or enter an arena they associate with the foot-shock.
So, the animal’s aversive behaviour becomes conditioned with the stimulus. Similarly, scientists can condition mice to expect
Scientists have even shown that this conditioned learning is so strong and pronounced, they can reproduce these behaviours by activating amygdala neurons after the learning trials took place.1
HOW DOES CONDITIONING DEVELOP IN THE AMYGDALA?
However, how this learning develops in the amygdala circuitry and is represented by individual neurons remained a mystery, until now. Recently, a group from Cold Spring Harbour Laboratory led by Prof. Bo Li published their findings in Nature
Li and his postdoc Xian Zhang conditioned the mice to associate fear with one type of tone by pairing it with a puff of air to the face. And they conditioned the mice to expect reward when another tone was played by giving the mice water.
CAN YOU IMAGE THE NEURAL BASIS OF CONDITIONING?
The scientists used mini microscopes to image the activity of basolateral amygdala neurons expressing the calcium reporter GCamp6 in mice. An increase in fluorescence denotes an increase in the influx of calcium in the neurons, which is a proxy for an increase in the cells’ activity. The scientists observed neurons under their mini microscopes as they played the sounds to the mice. The neurons that underlie learning of the association between the tones and the behaviour were activated in response to the tones.
They initially found that the neurons spiked randomly in response to the tones. However, with repeated trials some of the neurons’ activity became correlated with the playing of the tone. These
As the firing patterns became more specific, the animals licked in response to the reward-associated tone – anticipating water, and they blinked in response to the punishment-associated sound – anticipating an air puff.
IS IT POSSIBLE TO REVERSE CONDITIONING?
Most interesting of
The findings of this paper reveal a cool way by which individual neurons can be observed to correlate their activity with a stimulus. The advantage of using imaging techniques over electrophysiological techniques are that many neurons can be imaged at any one time, giving a population view of the neurons in the basolateral amygdala. However,
Deep tissue imaging approaches in awake behaving animals are the future of neuroscience research. It will be fascinating to see how this technology advances, as understanding how conditioned
Learn: New lens enables deep tissue imaging of dendrites in the hippocampus
New Pryer lens from MCI-Neuroscience enables deep tissue imaging in the brain.
1. Felix-Ortiz, A. C., Burgos-Robles, A., Bhagat, N. D., Leppla, C. A., & Tye, K. M. (2016). Bidirectional modulation of anxiety-related and social behaviors by amygdala projections to the medial prefrontal cortex. Neuroscience, 321, 197-209.
2. Zhang, X. and Li, B. (2018). Population coding of valence in the basolateral amygdala. Nature Communications, 9(1).