c-Jun-N-terminal kinase 1 is necessary for nicotine-induced enhancement of contextual fear conditioning

Abstract

Acute nicotine enhances hippocampus-dependent learning. Identifying how acute nicotine improves learning will aid in understanding how nicotine facilitates the development of maladaptive memories that contribute to drug-seeking behaviors, help development of medications to treat disorders associated with cognitive decline, and advance understanding of the neurobiology of learning and memory. The effects of nicotine on learning may involve recruitment of signaling through the c-Jun n-terminal kinase family (JNK 1-3). Learning in the presence of acute nicotine increases the transcription of mitogen-activated protein kinase 8 (Mapk8, also known as JNK1), likely through a CREB-dependent mechanism. The functional significance of JNK1 in the effects of acute nicotine on learning, however, is unknown. The current studies undertook a backward genetic approach to determine the functional contribution JNK1 protein makes to nicotine-enhanced contextual fear conditioning. JNK1 wildtype (WT) and knockout (KO) mice were administered acute nicotine prior to contextual and cued fear conditioning. 24 hours later, mice were evaluated for hippocampus-dependent (contextual fear conditioning) and hippocampus-independent (cued fear conditioning) memory. Nicotine selectively enhanced contextual conditioning in WT mice, but not in KO mice. Nicotine had no effect on hippocampus-independent learning in either genotype. JNK1 KO and WT mice given saline showed similar levels of learning. These data suggest that JNK1 may be recruited by nicotine and is functionally necessary for the acute effects of nicotine on learning and memory.

Acute nicotine disrupts consolidation of contextual fear extinction and alters long-term memory-associated hippocampal kinase activity

“…This suggests JNK1 may modulate the strength of memories. There is also evidence from our lab showing that hippocampal JNK1 phosphorylation is required for the acute nicotine-induced enhancement of contextual fear conditioning (Kenney et al, 2010; Leach et al, 2016). For example, acute nicotine upregulated the JNK1 mRNA in the hippocampus during the nicotine enhancement of contextual fear conditioning (Kenney et al, 2010).…”

“…For example, acute nicotine upregulated the JNK1 mRNA in the hippocampus during the nicotine enhancement of contextual fear conditioning (Kenney et al, 2010). Moreover, the acute nicotine-induced enhancement of contextual fear conditioning was absent in JNK1 KO mice (Leach et al, 2016). These results show that JNK1 may be critical for the nicotinic modulation of long-term memory formation.…”