Input from the medial geniculate nucleus modulates amygdala encoding of fear memory discrimination

Abstract

Generalization of fear can involve abnormal responding to cues that signal safety and is common in people diagnosed with post-traumatic stress disorder. Differential auditory fear conditioning can be used as a tool to measure changes in fear discrimination and generalization. Most prior work in this area has focused on elevated amygdala activity as a critical component underlying generalization. The amygdala receives input from auditory cortex as well as the medial geniculate nucleus (MgN) of the thalamus, and these synapses undergo plastic changes in response to fear conditioning and are major contributors to the formation of memory related to both safe and threatening cues. The requirement for MgN protein synthesis during auditory discrimination and generalization, as well as the role of MgN plasticity in amygdala encoding of discrimination or generalization, have not been directly tested. GluR1 and GluR2 containing AMPA receptors are found at synapses throughout the amygdala and their expression is persistently up-regulated after learning. Some of these receptors are postsynaptic to terminals from MgN neurons. We found that protein synthesis-dependent plasticity in MgN is necessary for elevated freezing to both aversive and safe auditory cues, and that this is accompanied by changes in the expressions of AMPA receptor and synaptic scaffolding proteins (e.g., SHANK) at amygdala synapses. This work contributes to understanding the neural mechanisms underlying increased fear to safety signals after stress.

Understanding the Effects and Adverse Reactions of Deep Brain Stimulation: Is It Time for a Paradigm Shift Toward a Focus on Heterogenous Biophysical Tissue Properties Instead of Electrode Design Only?

“…Moreover, 104.25 V/m of field strength (50%) additionally reaches the Hyp, the whole ic, the mmt, the fct, parts of the ml and GPi, the bic, the al, parts of the reticular thalamic nucleus (R) and the whole pulvinar (Pul), MGN and LGN. Given the fact that Figure 2 proves an unexpected extension of electrical current to geniculate thalamic and pulvinar areas, changes in emotion perception could be attributed to impaired visual and auditory processing ( Péron et al, 2010 , 2013 ; Symons et al, 2016 ; Ferrara et al, 2017 ).…”

Evaluation of medial division of the medial geniculate (MGM) and posterior intralaminar nucleus (PIN) inputs to the rat auditory cortex, amygdala, and striatum

“…Doubling the shock strength significantly increased the percentage of the units responding to both auditory stimuli, shifting the balance toward a greater proportion of generalizing over cue‐specific cells. These changes that translate to an elevated freezing response to both the paired and unpaired auditory stimulus appears to be dependent on protein synthesis‐dependent plasticity in medial geniculate and subsequent changes in the expressions of AMPA receptor and synaptic scaffolding proteins at their amygdala synapses (Ferrara, Cullen, Pullins, Rotondo, & Helmstetter, ). Clearly, a thorough understanding of the cells giving rise to these thalamoamygdalar projection from the MGM/PIN is vital to our understanding and treating such debilitating conditions.…”

Modulation of fear generalization by the zona incerta

“…The contributions of these brain regions have mostly been ignored in the context of fear-related behavior. At the level of the thalamus, studies have demonstrated that the auditory thalamus influences fear generalization (25,26) and that the paraventricular thalamus influences fear conditioning and fear memory retrieval (27,28). Most recently, the zona incerta (ZI), a sub-thalamic region, has received attention for its role in modulating defensive responses and retrieval of fear-related memories (29,30).…”