Abstract
The optogenetic manipulation of light-activated ion-channels/pumps (i.e., opsins) can reversibly activate or suppress neuronal activity with precise temporal control. Therefore, optogenetic techniques hold great potential to establish causal relationships between specific neuronal circuits and their function in freely moving animals. Due to the critical role of the hippocampal CA1 region in memory function, we explored the possibility of targeting an inhibitory opsin, ArchT, to CA1 pyramidal neurons in mice. We established a transgenic mouse line in which tetracycline trans-activator induces ArchT expression. By crossing this line with a CaMKIIα-tTA transgenic line, the delivery of light via an implanted optrode inhibits the activity of excitatory CA1 neurons. We found that light delivery to the hippocampus inhibited the recall of a contextual fear memory. Our results demonstrate that this optogenetic mouse line can be used to investigate the neuronal circuits underlying behavior.
Highlights
We showed that the recall of a fear memory in TetO-ArchT mice is reversibly inhibited by light delivery to the hippocampus, providing evidence of the utility of this new mouse line in memory research
To generate TetO-ArchT-green fluorescent protein (GFP) mice, the ArchT-GFP cDNA fragment was subcloned to a pTRE-Tight (Clontech) vector with an additional SV40 polyA sequence amplified from a pMSG vector (Pharmacia) as a template in front of the existing SV40 polyA signal
In situ hybridization revealed that transgene mRNA was widely expressed in the forebrain, including the cerebral cortex, hippocampus, striatum, olfactory bulb, and amygdala (Fig 1A– 1F), consistent with the reported distribution of tTA in the driver line [21]
Summary
Inhibiting CA1 Activity in ArchT Mouse Prevents Recall of Fear Memory We confirmed that light delivery reliably inhibits CA1 neuronal activity in vivo. We showed that the recall of a fear memory in TetO-ArchT mice is reversibly inhibited by light delivery to the hippocampus, providing evidence of the utility of this new mouse line in memory research.
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