Sessions

Synaptic connections in the hippocampal CA3 region play important roles in memory. The dorsal part of CA3 is associated with encoding spatial aspects, while the ventral part contributes to coding emotional memories. The synaptic connections from both parts target not only local postsynaptic neurons, but the axons of CA3 pyramidal cells usually cross to the opposite hemisphere, and also innervate large regions along the dorso-ventral axis. Understanding long-range connections is important, as nearly half of the output of CA3 pyramidal cells target the opposite hemisphere, and connections between dorsal and ventral CA3 regions link two functionally distinct regions. While previous research has revealed extensive knowledge about the local synaptic connections, we know much less about the long-range connections of the CA3 regions, including their synaptic target neurons and functional properties. Recent developments in voltage-indicators (proteins reporting changes in membrane voltage as fluorescence changes) allowed optical measurements of small voltage changes in large numbers of neurons. And, combination of voltage imaging with optogenetic stimulators (light activated ion channels) enabled the activation of axons originating from well-defined presynaptic cell populations. In this work I used the Voltron2 voltage-indicator and the Channelrhodopsin2 optogenetic stimulator to investigate the functional properties of synaptic connections from CA3 pyramidal cells onto distal CA3 pyramidal cells and interneurons.

My results showed that contralateral CA3-CA3 synaptic connections show specific arrangements along the dorso-ventral and the ipsilateral-contralateral axes. Specifically, the dorsal CA3 innervated the ventral CA3 extensively, while fibers originating from ventral CA3 avoided the dorsal CA3. This suggests a preferred direction of information flow between the two functionally distinct regions along the dorso-ventral axis. I also found that the amplitudes of postsynaptic responses evoked by dorsal CA3 fibers were larger, and more likely elicited postsynaptic firing compared to fibers from the ventral CA3 region. Furthermore, the results showed that contralateral dorsal fibers targeted more inhibitory interneurons than pyramidal cells; whereas, ventral CA3 fibers targeted primarily pyramidal cells in both hemispheres suggesting a direction-specificity control of activity.

Overall, our all-optical approach provides an efficient tool for functional mapping the output of large numbers of identified neurons onto a large number of putative postsynaptic cells simultaneously. As a result, I was able to describe the characteristics of synaptic connections that were previously unknown. These results revealed that both direct excitation between CA3 pyramidal cells and the feedforward inhibition show region-specific properties.