Proximodistal Heterogeneity of Hippocampal CA3 Pyramidal Neuron Intrinsic Properties, Connectivity, and Reactivation during Memory Recall
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. Her...
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Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2017-08, Vol.95 (3), p.656-672.e3 |
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Zusammenfassung: | 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.
•CA3 shows a marked proximodistal gradient in intrinsic and synaptic properties•Mossy fiber and direct cortical inputs show opposing gradients of synaptic strength•CA3b has the strongest recurrent excitation because of reduced inhibition•This connectivity can explain robust CA3b reactivation during fear memory retrieval
Sun et al. report marked proximodistal gradients in dorsal CA3 neuron intrinsic excitability and synaptic connectivity, with a reduced recurrent I/E ratio in mid-CA3 (CA3b) leading to its stronger net excitation and memory reactivation. This study complements recent findings on CA3 heterogeneity in spatial encoding and behaviors. |
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ISSN: | 0896-6273 1097-4199 |
DOI: | 10.1016/j.neuron.2017.07.012 |