Fear Learning Enhances Neural Responses to Threat-Predictive Sensory Stimuli

Abstract

The central nervous system rapidly learns that particular stimuli predict imminent danger. This learning is thought to involve associations between neutral and harmful stimuli in cortical and limbic brain regions, though associative neuroplasticity in sensory structures is increasingly appreciated. We observed the synaptic output of olfactory sensory neurons (OSNs) in individual mice before and after they learned that a particular odor indicated an impending footshock. OSNs are the first cells in the olfactory system, physically contacting the odor molecules in the nose and projecting their axons to the brain’s olfactory bulb. Surprisingly, OSN output evoked by the shock-predictive odor was selectively facilitated after fear conditioning. These results indicate that affective information about stimuli can be encoded in their very earliest representations in the nervous system.

Information Theory, Memory, Prediction, and Timing in Associative Learning

“…Results from fear conditioning in mice (Ryan, Roy et al 2015) and gill-withdrawal conditioning in Aplysia (Chen, Cai et al 2014) suggest that the acquired information in fear conditioning is not encoded in the altered synaptic conductances themselves but rather within the postsynaptic neurons. Results from olfactory fear conditioning in mice show that the learned predictive power of one odor versus other non-predictive odors is manifest in differential transmitter release in the olfactory glomeruli from first-order olfactory neurons (Kass, Rosenthal et al 2013). …”

Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

“…Within our model, olfactory fear conditioning leading to an enhanced number of CS-responsive OSNs may serve to enhance the animals' sensitivity to an important environmental cue, whereas following olfactory fear extinction, the accompanying decrease in CS-responsive OSNs may lead to a decrease in overall sensitivity to an extinguished odor. Complementary work in adult rodent systems has shown neurophysiological evidence of an in vivo odor-specific enhancement in the synaptic output of OSNs following an associative learning event (6). Thus, whereas regions such as the amygdala, hippocampus, or prefrontal cortex may allow for the inhibition of fear expression or the modulation of that inhibition (12,21), the primary olfactory sensory system likely plays a major role in the CS sensitivity and responsiveness following a learning event and its extinction.…”

“…Postmitotic organizational changes, along with activity-dependent plasticity, have been largely implicated in shaping sensory circuits from development through adulthood (1)(2)(3)(4). In particular, the olfactory sensory system of adult mice exhibits functional and neuroanatomical learning-dependent changes following olfactory fear conditioning in adulthood (5)(6)(7). The M71-LacZ transgenic mouse line expresses LacZ under the M71 odorant receptor (OR) promoter (encoded by the olfactory receptor 151 gene, Olfr151) (8) in the M71 OR-expressing, acetophenone-responsive population of olfactory sensory neurons (OSNs).…”

Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling

“…Fear conditioning was carried out as described previously (32,76). Mice were placed into a square chamber with a grid floor.…”