Cellular and Oscillatory Substrates of Extinction Learning
Davis, Patrick.
2019
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Abstract: In contrast to the hard-wired components characteristic of
electronic circuits and some invertebrate nervous systems, mammalian brains contain
modifiable elements within circuits that are capable of both robustness and remarkable
adaptability. This balance is exemplified by the capacity of mammals to both learn and
update previously formed associations, and to select from opposing be... read morehavioral strategies
based on a diversity of previous experience. A classic example of this is the paradigm of
contextual fear conditioning and extinction learning, whereby an animal first forms a
fearful association with a conditioned context, but subsequently learns that the context is
safe. Because these two learning processes have distinct and opposing behavioral
consequences, this paradigm grants experimental access to the features of the brain which
enable both the formation of an associative memory and the subsequent modification of that
memory with continued experience, as well as to the circuits which govern ultimate
behavioral output. To date, the mechanisms underlying the modification of associative fear
memories through extinction learning have yet to be completely understood. Using a novel
combination of chemo- and optogenetics, activity-based neuronal-ensemble labeling, circuit
tracing, and in vivo¬ electrophysiology, we have identified cellular and oscillatory
substrates of fear extinction learning that depend critically on parvalbumin (PV)-
expressing interneurons in the basolateral amygdala (BLA). Specifically, we found that
extinction learning confers PV- interneurons in the BLA with a dedicated role in the
suppression of a previously encoded fear memory via selective suppression of BLA
fear-encoding neurons. BLA PV-interneurons are positioned to gate reciprocal communication
between BLA and medial prefrontal cortex (mPFC), and their activity controls the activation
of spatially localized and functionally opposing ensembles within mPFC. We establish that
BLA PV-interneurons are critical to the generation of two opposing oscillatory states
across the mPFC-BLA circuit. Extinction learning modifies the relationship between these
two states to allow for "competition" between them. Artificial induction of these
oscillatory states by direct manipulation of PV-interneurons is sufficient to elicit
bidirectional, learning-dependent control over mPFC-BLA circuit coordination and fear
behavior. Finally, we provide evidence potentially linking these circuit oscillatory
properties with ensemble data through the phenomenon of resonance. These findings identify
cellular and oscillatory substrates of fear extinction learning that critically depend on
BLA PV-interneurons. The role of the BLA PV-network in mediating interactions between
previously learned functional network states and memory-encoding ensembles is likely to be
broadly applicable to interneuron microcircuit function in both physiological and
pathological states.
Thesis (Ph.D.)--Tufts University, 2019.
Submitted to the Dept. of Neuroscience.
Advisor: Jamie Maguire.
Committee: Thomas Biederer, and Yongjie Yang.
Keyword: Neurosciences.read less - ID:
- wh247533g
- Component ID:
- tufts:25409
- To Cite:
- DCA Citation Guide EndNote
