Summary
The hippocampal CA3 region is classically viewed as a homogeneous
autoassociative network critical for associative memory and pattern completion.
However, recent evidence has demonstrated a striking heterogeneity along the
transverse, or proximodistal, axis of CA3 in spatial encoding and memory. Here
we report the presence of striking proximodistal gradients in intrinsic membrane
properties and synaptic connectivity for dorsal CA3. A decreasing gradient of
mossy fiber synaptic strength along the proximodistal axis is mirrored by an
increasing gradient of direct synaptic excitation from entorhinal cortex.
Furthermore, we uncovered a nonuniform pattern of reactivation of fear memory
traces, with the most robust reactivation during memory retrieval occurring in
mid-CA3 (CA3b), the region showing the strongest net recurrent excitation. Our
results suggest that heterogeneity in both intrinsic properties and synaptic
connectivity may contribute to the distinct spatial encoding and behavioral role
of CA3 subregions along the proximodistal axis.
Synaptic inputs from different brain areas are often targeted to distinct regions of neuronal dendritic arbors. Inputs to proximal dendrites usually produce large somatic EPSPs that efficiently trigger action potential (AP) output, whereas inputs to distal dendrites are greatly attenuated and may largely modulate AP output. In contrast to most other cortical and hippocampal neurons, hippocampal CA2 pyramidal neurons show unusually strong excitation by their distal dendritic inputs from entorhinal cortex (EC). In this study, we demonstrate that the ability of these EC inputs to drive CA2 AP output requires the firing of local dendritic Na+ spikes. Furthermore, we find that CA2 dendritic geometry contributes to the efficient coupling of dendritic Na+ spikes to AP output. These results provide a striking example of how dendritic spikes enable direct cortical inputs to overcome unfavorable distal synaptic locale to trigger axonal AP output and thereby enable efficient cortico-hippocampal information flow.DOI:
http://dx.doi.org/10.7554/eLife.04551.001
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.