My Project

What I am studying

The hippocampus is a brain structure that is involved in memory formation, where inputs (contextual information) are processed here and converted to outputs (firing of pyramidal cells). The firing of pyramidal cells are regulated by more than 20 types of inhibitory interneurons, and we still don't know exactly how this works.

I am studying one type of interneuron, called the neurogliaform cells (NGFCs), to see how they function within the hippocampal circuit. NGFCs form synapses onto the distal tufts of pyramidal cell apical dendrites alongside excitatory inputs from the entorhinal cortex. NGFCs also express neuronal nitric oxide synthase (nNOS), are often synaptically coupled, and fire during theta oscillations in vivo.

Show image of hippocampal interneuron subtypes

Peter Somogyi and Thomas Klausberger, The Journal of Phsyiology, 2005

What I have found, a summary

I found that when theta-associated activity patterns were evoked in NGFCs in rat hippocampal slices, the cells showed a transient reduction in unitary IPSP amplitude. This "firing-induced suppression of inhibition" (FSI) required back-propagation of action potentials, calcium influx through L-type calcium channels, nNOS activity, and activation of NO-sensitive guanylyl cyclase (NO-sGC) receptors, which are present on presynaptic terminals. FSI also indirectly increased the amplitude of EPSPs. Thus FSI may enhance spatial and temporal summation of excitatory inputs to NGFCs, thus regulating their inhibition of pyramidal cells.

1. In vivofiring induces suppresion of inhibition (FSI)

Injection of in vivo firing pattern into the postsynaptic cell induces FSI. FSI requires action potential to be triggered and subthrehold firing pattern cannot trigger FSI.

The suppresion is proportional, suggesting it is likely to be a presynaptic mechanism and due to retrograde signalling which were realeased during postsynaptic cell firing.

2. What happens during firing?

I found that action potentials backpropagate in these neurons, here is a video of a recording done with Voltage Imaging.

In addition, using Calcium Imaging I have found that cell pairs showing FSI have higher dendritic calcium level. Possibly due to backpropating action potential activates dendritic calcium channels.

Using pharmcology I have found this calcium influx is indeed through calcium channels (L-type) and not from stores.

3. Which messenger(s) is responsible for FSI?

Using pharmacology I have found that nitric oxide is responsible for FSI. FSI is blocked by the application of the nNOs inhibitor L-NAME, NOs-GC antogonist ODQ, and potentiated by the nitric oxide precursor L-arginine.

4. Physiological implication of FSI

Using dynamic clamp, I found that FSI indirectly increase the amplitude of EPSPs as FSI reduces inhibition from interneurons