Abstract
Sparse populations of neurons in the dentate gyrus (DG) of the hippocampus are causally implicated in the encoding of contextual fear memories. However, engram-specific molecular mechanisms underlying memory consolidation remain largely unknown. Here we perform unbiased RNA sequencing of DG engram neurons 24 h after contextual fear conditioning to identify transcriptome changes specific to memory consolidation. DG engram neurons exhibit a highly distinct pattern of gene expression, in which CREB-dependent transcription features prominently (P = 6.2 × 10-13), including Atf3 (P = 2.4 × 10-41), Penk (P = 1.3 × 10-15), and Kcnq3 (P = 3.1 × 10-12). Moreover, we validate the functional relevance of the RNAseq findings by establishing the causal requirement of intact CREB function specifically within the DG engram during memory consolidation, and identify a novel group of CREB target genes involved in the encoding of long-term memory.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Activating Transcription Factor 3 / genetics
-
Activating Transcription Factor 3 / metabolism
-
Animals
-
Conditioning, Psychological / physiology
-
Cyclic AMP Response Element-Binding Protein / metabolism*
-
Cytoskeletal Proteins / metabolism*
-
Dentate Gyrus / cytology
-
Dentate Gyrus / physiology*
-
Enkephalins / genetics
-
Enkephalins / metabolism
-
Fear / physiology
-
Gene Expression Profiling / methods
-
Gene Expression Regulation / physiology
-
KCNQ3 Potassium Channel / genetics
-
KCNQ3 Potassium Channel / metabolism
-
Male
-
Memory Consolidation / physiology*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Transgenic
-
Models, Animal
-
Nerve Tissue Proteins / metabolism*
-
Neurons / metabolism
-
Protein Precursors / genetics
-
Protein Precursors / metabolism
-
Sequence Analysis, RNA
-
Stereotaxic Techniques
Substances
-
Activating Transcription Factor 3
-
Atf3 protein, mouse
-
Creb1 protein, mouse
-
Cyclic AMP Response Element-Binding Protein
-
Cytoskeletal Proteins
-
Enkephalins
-
KCNQ3 Potassium Channel
-
Kcnq3 protein, mouse
-
Nerve Tissue Proteins
-
Protein Precursors
-
activity regulated cytoskeletal-associated protein
-
preproenkephalin