Prefrontal activity links nonoverlapping events in memory - PubMed (original) (raw)

Marieke R Gilmartin et al. J Neurosci. 2013.

Abstract

The medial prefrontal cortex (mPFC) plays an important role in memory. By maintaining a working memory buffer, neurons in prelimbic (PL) mPFC may selectively contribute to learning associations between stimuli that are separated in time, as in trace fear conditioning (TFC). Until now, evidence for this bridging role was largely descriptive. Here we used optogenetics to silence neurons in the PL mPFC of rats during learning in TFC. Memory formation was prevented when mPFC was silenced specifically during the interval separating the cue and shock. Our results provide support for a working memory function for these cells and indicate that associating two noncontiguous stimuli requires bridging activity in PL mPFC.

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Figures

Figure 1.

Figure 1.

Laser illumination silences ArchT-expressing neurons in PL mPFC. a, Expression of AAV9/CAG-ArchT-GFP in layers 2/3 and 5/6 of PL and coexpression with the neuronal marker NeuN. Scale bar, 20 μm. b, Multi-unit activity recorded in PL showing population silencing during 20 s laser epochs in a rat recorded 3 weeks after virus injection (532 nm, 12 mW; green bar). c, Action potential events of individual units recorded at two different depths in PL showing silencing during two 20 s laser presentations. d, Peri-event time histograms of three representative units from c (same color) showing the change in firing to laser onset and offset. Each bar represents the number of spikes in 1 s bins averaged across eight 20 s laser presentations. The majority of units recorded did not show rebound activity at laser offset, but some units (1 of 7 units in c; d, right) exhibited brief rebound activity. e, Normalized firing of all PL units recorded from the probe shank centered below the optic fiber (n = 59) across eight laser presentations showing the mean change in firing (±SEM) to laser onset (green bar) relative to baseline. The inset shows the mean change in firing to laser offset.

Figure 2.

Figure 2.

Temporally specific silencing of PL mPFC during conditioning. a, Coronal diagrams show the placement of fiber tips in PL for each rat. b, ArchT expression in PL mPFC and location of bilateral fiber cannulae in PL. c, Procedure diagram of light delivery (green bar) for each training group during conditioning. d, Mean freezing during the training session of TFC. Each point shows the freezing during each trial (10 s CS and 20 s trace interval). For the Trial, CS, and Trace Interval groups, the laser was on for all or part (CS group) of this period. The unpaired group received the first CS trial after two UCS trials. Freezing during each of the six CS trials is shown in the inset. All groups, including unpaired, showed equivalent freezing on the final trial (F(5,24) = 0.321, p = 0.895). Coronal diagrams were adapted from Paxinos and Watson, 2007, with permission from Elsevier.

Figure 3.

Figure 3.

Silencing PL mPFC during the trace interval impairs learning the CS–UCS association across a temporal gap. a, b, Mean freezing during the CS (a) and context tests on the day following training (b). Rats that received light during the trace interval or whole trial during conditioning exhibited impaired CS memory at test, relative to ITI Control rats (*p < 0.05). Contextual fear conditioning was intact.

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