Each neuron in the central nervous system has a substantial dendritic tree that receives input from the majority of the thousands of synapse on the neuron. Synaptic inputs interact with one another, with the passive electrical structure of the dendrites, and with voltage-gated channels in the dendrites, soma, and axon in a complex process, often referred to as synaptic integration. These electrical interactions, occurring largely in the dendritic tree, determine whether at a given time a neuron sends a signal to its network partners via an action potential propagation down the axon. Dendrites therefore have a prominent role in determining the function of a neuron in its network, yet relatively little is known about their electrical properties, in part due to their small size, which has rendered dendrites difficult to record from. Recently, however, techniques have been developed that allow patch-pipette recordings to be made routinely from the dendrites of neurons in brain slices. The experiments proposed here make use of this technique, often using simultaneous recordings from two points on the same neuron, with the goal of better understanding the process of synaptic integration in the dendrites of hippocampal pyramidal neurons. Simultaneous patch-pipette recordings from the soma and dendrites of hippocampal CA1 pyramidal neurons have revealed that action potentials are initiated near the soma of these neurons. It is therefore critical to know how much synaptic potentials are attenuated as they propagate from the dendrites toward the soma, in order to understand how effective dendritic synapses are at producing action potential firing. This question will be addressed by directly examining the attenuation of synaptic potentials between dendritic and somatic recording sites. As synaptic potentials propagate from the dendrites toward the soma, however, they may be affected by dendritic voltage-gated channels activated by the synaptic depolarization. The contribution of such channels to the propagation of EPSPs will therefore be studied by examining the effects of various channel blockers on the propagation of """"""""EPSPs"""""""", simulated by using current injection in the shape of an EPSC through a dendritic patch pipette. Furthermore, to understand the role of hyperpolarization and shunting inhibition on the propagation of EPSPs from the dendrites to the soma, the effects of current injections mimicking IPSCs, or local application of GABA to dendrites, will be examined. Together with information concerning the roles of dendritic voltage-gated channels and inhibition in shaping EPSP propagation, the detailed description of voltage propagation in the dendrites of hippocampal neurons will be used to construct realistic compartmental propagation models of neurons that should prove useful to investigators examining the role of these neurons in neural networks responsible for the processes of learning and memory.
Showing the most recent 10 out of 28 publications
