Object-location training elicits an overlapping but temporally distinct transcriptional profile from contextual fear conditioning

Abstract

Hippocampus-dependent learning is known to induce changes in gene expression, but information on gene expression differences between different learning paradigms that require the hippocampus is limited. The bulk of studies investigating RNA expression after learning use the contextual fear conditioning task, which couples a novel environment with a footshock. Although contextual fear conditioning has been useful in discovering gene targets, gene expression after spatial memory tasks has received less attention. In this study, we used the object-location memory task and studied gene expression at two time points after learning in a high-throughput manner using a microfluidic qPCR approach. We found that expression of the classic immediate-early genes changes after object-location training in a fashion similar to that observed after contextual fear conditioning. However, the temporal dynamics of gene expression are different between the two tasks, with object-location memory producing gene expression changes that last at least 2 hours. Our findings indicate that different training paradigms may give rise to distinct temporal dynamics of gene expression after learning.

Keywords: Fear conditioning; Hippocampus; Object-location memory; Spatial memory; Transcription.

Figure 1. Classic IEGs Show Expected Expression Changes after OLM Training

Sixteen genes that are known to be induced 30 minutes after contextual fear conditioning were studied 30 minutes after OLM training. Each gene tested displayed the expression change that would be expected after contextual fear conditioning indicating these genes may represent a common transcriptional response to learning. All error bars denote s.e.m. and * indicates p<0.01.

Figure 2. Limited Expression Changes of Nuclear Receptors after OLM training

Because of the known involvement of the Nr4a nuclear receptor family in memory, we tested expression of all nuclear receptors expressed in the hippocampus 30 minutes after OLM training. The Nr4a family displayed increased expression after OLM, while NR1D1, NR2F2, and RXRg had reduced expression. All error bars denote s.e.m. and * indicates p<0.01.

Figure 3. Modifiers of Histone Acetylation Display Limited Regulation after OLM Training

Histone modifying enzymes were tested for expression changes 30 minutes after OLM training. (A) Hdac7, a class IIa HDAC, was the only family member found to change expression after OLM. (B) No HATs were observed to change expression after OLM. All error bars denote s.e.m. and * indicates p<0.01.

Figure 4. No Changes in Other Transcriptional Regulators after OLM Training

Other genes that can regulate gene expression, including DNMTs, were tested 30 minutes after OLM training. No differences in any gene were observed. All error bars denote s.e.m. and * indicates p<0.01.

Figure 5. OLM Training Induces Long-Lasting Changes in Gene Expression Not Seen after Fear Conditioning

(A) Every gene was also tested 2 hours after OLM training to observe the maintenance of transcription. Genes shown in this figure are those that were changed at 2 hours after OLM, all other genes were unchanged. Sin3a was the only gene uniquely regulated at the 2 hour time point. (B) These same genes do not show gene expression changes 2 hours after contextual fear conditioning. All error bars denote s.e.m. and * indicates p<0.01.