ABL1 in thalamus is associated with safety but not fear learning

Mouna R Habib,Ira K Katz,Raphael Lamprecht,Dan A Ganea

doi:10.3389/fnsys.2013.00005

Abstract

In auditory fear conditioning a tone is paired with a footshock, establishing long lasting fear memory to the tone. In safety learning these stimuli are presented in an unpaired non-overlapping manner and enduring memories to the tone as a safety signal are formed. Although these paradigms utilize the same sensory stimuli different memories are formed leading to distinct behavioral outcome. In this study we aimed to explore whether fear conditioning and safety learning lead to different molecular changes in thalamic area that receives tone and shock inputs. Toward that end, we used antibody microarrays to detect changes in proteins levels in this brain region. The levels of ABL1, Bog, IL1B, and Tau proteins in thalamus were found to be lower in the group trained for safety learning compared to the fear conditioning group 6 h after training. The levels of these proteins were not different between safety learning and fear conditioning trained groups in auditory cortex. Western blot analysis revealed that the ABL1 protein level in thalamus is reduced specifically by safety learning but not fear conditioning when compared to naïve rats. These results show that safety learning leads to activation of auditory thalamus differently from fear conditioning and to a decrease in the level of ABL1 protein in this brain region. Reduction in ABL1 level in thalamus may affect neuronal processes, such as morphogenesis and synaptic efficacy shown to be intimately regulated by changes in this kinase level.

Highlights

Fear conditioning leads to long-term fear memory formation and is a model of psychopathologies conditions such as anxiety and post-traumatic stress disorders (e.g., LeDoux, 2000)
Paired tone-shock presentation leads to fear memory of the tone (Fanselow and LeDoux, 1999; LeDoux, 2000; Davis and Whalen, 2001; Sah et al, 2003; Maren, 2005) whereas unpaired training leads to safety learning where the rats remember the CS as a safety signal that predicts the absent of the shock (Rogan et al, 2005; Pollak et al, 2008; Ostroff et al, 2010)
In this study we find that safety learning, but not fear conditioning, leads to reduction of ABL1 protein level in a thalamic region that includes areas that process the tone and shock information

Summary

Introduction

Fear conditioning leads to long-term fear memory formation and is a model of psychopathologies conditions such as anxiety and post-traumatic stress disorders (e.g., LeDoux, 2000). We explored whether fear conditioning and safety learning lead to different molecular responses in the auditory thalamus which transfers information to both LA and CP during fear and safety learning (LeDoux, 2000; Rogan et al, 2005). Lesion to the auditory thalamus post training impaired the ability to inhibit fear in the presence of the noise safety signal (Heldt and Falls, 2006) and changes in CS response after safety learning in LA and CP is consistent with modulation of CS information arriving via a direct thalamic projection from MGm/PIN (posterior intralaminar nucleus) (Rogan et al, 2005). Convergence of auditory and footshock responses was detected in these areas

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Conclusion