No abstract

A potentially vital pathway in the processing of spatial memory is the pathway from ventral hippocampus to medial prefrontal cortex (vHPC-mPFC). To assess long-term potentiation (LTP) induction and maintenance across days in this pathway, the effects of several induction paradigms were compared in awake, freely moving rats. Two different high-frequency stimulation (HFS) protocols generated LTP lasting no longer than 1 week. However, after delivering HFS on three consecutive days, LTP lasted an average of 20 days, due mainly to the greater initial induction. Thus the pathway does not require extensive multi-day stimulation to induce LTP, as for other intra-neocortical pathways, but also it does not exhibit the extremely long-lasting and stable LTP previously observed in area CA1 and the dentate gyrus. By using bilaterally placed stimulating and recording electrodes, we found that HFS in one vHPC generated responses and LTP in the contralateral mPFC, even when the ipsilateral mPFC was inactivated by CNQX. We attribute this crossed response to a polysynaptic pathway from the vHPC to the contralateral mPFC. Finally, we found that repeated overnight exposure to an enriched environment also potentiated the vHPC-mPFC response, but this too was a transient effect lasting < 9 days, declining to baseline even before the enriched environment treatment was completed. Overall, these findings are consistent with the view that potentiation of vHPC-mPFC pathway may play a key role in promoting the hippocampus-mPFC interplay that, over days, leads to long-term storage in the frontal cortex of memories that are independent of the hippocampus.

There is evidence that besides limbic brain structures, prefrontal and insular cortical activations and deactivations are involved in the pathophysiology of panic disorder. This study investigated activation response patterns to stimulation with individually selected panic-specific pictures in patients with panic disorder with agoraphobia (PDA) and healthy control subjects using functional magnetic resonance imaging (fMRI). Structures of interest were the prefrontal, cingulate, and insular cortex, and the amygdalo-hippocampal complex. Nineteen PDA subjects (10 females, 9 males) and 21 healthy matched controls were investigated using a Siemens 3-Tesla scanner. First, PDA subjects gave Self-Assessment Manikin (SAM) ratings on 120 pictures showing characteristic panic/agoraphobia situations, of which 20 pictures with the individually highest SAM ratings were selected. Twenty matched pictures showing aversive but not panic-specific stimuli and 80 neutral pictures from the International Affective Picture System were chosen for each subject as controls. Each picture was shown twice in each of four subsequent blocks. Anxiety and depression ratings were recorded before and after the experiment. Group comparisons revealed a significantly greater activation in PDA patients than control subjects in the insular cortices, left inferior frontal gyrus, dorsomedial prefrontal cortex, the left hippocampal formation, and left caudatum, when PA and N responses were compared. Comparisons for stimulation with unspecific aversive pictures showed activation of similar brain regions in both groups. Results indicate region-specific activations to panic-specific picture stimulation in PDA patients. They also imply dysfunctionality in the processing of interoceptive cues in PDA and the regulation of negative emotionality. Therefore, differences in the functional networks between PDA patients and control subjects should be further investigated.