Article Figures & Data
Figures
- Figure 1.
Fear conditioning increases ERK phosphorylation in the entorhinal cortex 90 min after training. A, Representative photomicrographs showing the areas for cell counting after training (n = 6) or tone-context (control) exposure (n = 7). B, C, Summary of phospho-ERK-positive profile counts at 10× (B) and cell counts in MEA using unbiased stereology (C). D, E, Representative confocal photomicrographs of phospho-ERK (red)-NeuN (D) or GAD67 (E) double staining in the EC. Arrows mark double staining (D); arrowheads mark nondouble-stained cells; red arrowheads mark phospho-ERK-positive cells, and green arrowheads mark GAD67-positive cells (E). VIE, Ventral intermediate entorhinal; DIE, dorsal intermediate entorhinal; DLE, dorsal lateral entorhinal. Data indicate mean ± SEM; *p < 0.05.
- Figure 2.
Intraentorhinal infusion of PD098059 or UO126 decreases phospho-ERK immunoreactivity (A, F) but not NeuN immunoreactivity (B, G) in the entorhinal cortex and does not affect phospho-ERK immunoreactivity in the dorsal hippocampus (C, H), ventral subiculum (D, I), or ventral hippocampus (E, J) compared with the vehicle-infused contralateral side. Scale bars, 50 μm.
- Figure 3.
Blockade of ERK-mediated plasticity in the EC results in increased freezing and anticipatory behavior. A, Unique infusion sites for all behavioral experiments shown on coronal atlas plates adapted from Swanson (2004). Freezing behavior during the context-retention test after intra-ECPD098059 or vehicle infusion 40 min after training, shown binned into 30 sec time windows (PD098059, n = 6; vehicle, n = 7) (B) and after intra-ECPD098059, UO126, or vehicle infusion 40 min after training (PD098059, n = 15; UO126, n = 7; vehicle, n = 14) (C). Control animals given six training trials demonstrate increased freezing and anticipatory freezing similar to EC-drug-infused animals (n = 12) (D). Intra-EC infusion of PD098059 10 min after training does not affect freezing behavior during retention testing (PD098059, n = 8; vehicle, n = 8) (E). TR, Transition area. Data indicate mean ± SEM; *p < 0.05.
- Figure 4.
Simplified diagram of the circuitry underlying the freezing response. During fear conditioning, contextual information from the hippocampus (HIP) and EC is associated with the shock in the basal nucleus (B) of the amygdala (AMY). The perirhinal (PRh) cortex and prefrontal cortex (PFC) are thought to be involved in timing and input onto excitatory neurons (E) in the basal and lateral (L) nuclei and onto inhibitory GABAergic intercalated cells (ITC). Tone information enters L via the auditory thalamus and cortex (Aud TH/CX). The central nucleus (C) controls freezing behavior via activation of neurons in the periaqueductal gray (PAG). Blockade of ERK activity in the EC could decrease feedforward inhibition via decreased activation of inhibitory interneurons (I) in B, leading to increased freezing. Intra-EC ERK blockade could also indirectly increase the influence of PRh and PFC inputs on behavior, leading to anticipatory freezing. Arrows indicate excitatory connections, and the filled circle indicates inhibitory connections.
