|Ph.D Student||Sandler Maya|
|Subject||Synaptic Processing in Fine Tuft Dendrites of Layer 5|
Neocortical Pyramidal Neurons of the Rat
|Department||Department of Medicine||Supervisor||Professor Jackie Schiller|
|Full Thesis text|
Layer 5 thick tufted pyramidal neurons (L5ttPNs) in the rat somatosensory cortex receive and integrate many inputs and produce the major output signal to sub cortical areas. Until out work the tuft dendrites of these neurons were almost not explored due to technical difficulties of recording from such distal and thin objects. The excitatory postsynaptic potentials (EPSP) in tuft dendrites are expected to attenuated strongly as they forward propagate toward the soma and are unlikely to affect the cell's output. This enigma led us to focus on synaptic integration and plasticity in tuft dendrites.
In the first part of this work we examine the active mechanisms of tuft dendrites using focal stimulation. Our findings indicate that tuft dendrites are capable of eliciting dendritic N-methyl-D-aspartate (NMDA) spikes. We propose a three-layer model in the neurons: first, integration at tuft dendrites initiates NMDA spikes. Second, dendritic calcium spike is initiated around the main bifurcation of the apical dendrite. Third, action potential is initiated at the axon hillock. Therefore, NMDA spikes in tuft dendrites may play a critical role in affecting the cell's output.
In the second part of this work we examined plasticity rules at L5ttPNs' tuft dendrites. In order to investigate the possibility of Hebbian plasticity in tuft dendrites, we investigated the efficiency of back propagating action potentials (BAPs), back propagating dendritic calcium spikes (BCaSs) and NMDA spikes along tuft dendrites. We found that BAPs and BCaSs attenuated as they propagated to higher order branches. However, while BAP decreased tremendously, BCaS reached the most distal parts of tuft dendrites. We also identified two sub-groups of L5ttPNs according to their poor or efficient BCaS along tuft dendrites. Our data indicated that NMDA spikes were local to the activated branch. These findings suggest plausible different plasticity mechanisms.
In the third part of this work we investigated different plasticity mechanisms in tuft dendrites. We examined the effect of NMDA spikes alone and in coincidence with 2 unitary EPSP and found that NMDA spike induced an amplification of EPSP amplitude. We have also found a unique tuft plasticity following a very low frequency (0.1 Hz) stimulation of unitary EPSPs. Synaptic potentiation manifested in significant increase of EPSP amplitude as well as of BAPs and BCaS to tuft branches. Our data showed that this plasticity was NMDAR and Kv4.2 dependent, required internalization of membrane proteins and resulted in an insertion of AMPARs to the activated synapses.
In conclusion, our work started to unravel the exceptional tuft dendrites of L5ttPNs, in which: local NMDA spikes are the main active mechanism in tuft branches and may affect the neurons' output as well as participate in plasticity; BCaSs (and to a lesser extent BAPs) may reach distal parts of tuft dendrites, thus can possibly participate in Hebbian plasticity; low frequency plasticity induces an increase in EPSP amplitude as well as an increase in intrinsic properties. This work only began to reveal the mechanisms in tuft dendrites and more work is needed to decipher the network complexity in behaving animals.