Increasing CREB in the auditory thalamus enhances memory and generalization of auditory conditioned fear.
Although the lateral nucleus of the amygdala (LA) is essential for conditioned auditory fear memory, an emerging theme is that plasticity in multiple brain regions contributes to fear memory formation. The LA receives direct projections from the auditory thalamus, specifically the medial division of the medial geniculate nucleus (MGm) and adjacent posterior intralaminar nucleus (PIN). While traditionally viewed as a simple relay structure, mounting evidence implicates the thalamus in diverse cognitive processes. We investigated the role of plasticity in the MGm/PIN in auditory fear memory. First we found that auditory fear conditioning (but not control manipulations) increased the levels of activated CREB in both the MGm and PIN. Next, using viral vectors, we showed that exogenously increasing CREB in this region specifically enhanced formation of an auditory conditioned fear memory without affecting expression of an auditory fear memory, formation of a contextual fear memory, or basic auditory processing. Interestingly, mice with increased CREB levels in the MGm/PIN also showed broad auditory fear generalization (in contrast to control mice, they exhibited fear responses to tones of other frequencies). Together, these results implicate CREB-mediated plasticity in the MGm/PIN in both the formation and generalization of conditioned auditory fear memory. Not only do these findings refine our knowledge of the circuitry underlying fear memory but they also provide novel insights into the neural substrates that govern the degree to which acquired fear of a tone generalizes to other tones.
Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Jin-Hee
JH
Han
Adelaide P
AP
Yiu
Christina J
CJ
Cole
Hwa-Lin
HL
Hsiang
Rachael L
RL
Neve
Sheena A
SA
Josselyn
D000818:Animals; D001303:Auditory Cortex / Q000502:physiology*; D001307:Auditory Perception / Q000502:physiology*; D050882:CREB-Binding Protein / Q000502:physiology*; D003213:Conditioning, Psychological; D005239:Fear; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology; D013788:Thalamus / Q000502:physiology*
D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse