Chapter 13 Somato-dendritic processing of postsynaptic potentials I: Passive properties of dendrites From Cellular and Molecular Neurophysiology, Fourth Edition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Figure 13.1 Schematic of a neuron and some of its afferents. Afferent fibers establish synaptic contacts on spines and dendritic branches which are situated at different distances from the soma of the postsynaptic neuron. When these afferents are activated, the depolarizing or hyperpolarizing postsynaptic currents are conducted towards the soma and initial segment of the axon. It is at this level that the response of the postsynaptic neuron is generated. The response is then conducted along the axon and its collateral branches. From Cellular and Molecular Neurophysiology, Fourth Edition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Figure 13.2 Theoretical model of decremental conduction of excitatory postsynaptic potentials (EPSP) along dendrites. (a) Four EPSPs numbered 1 to 4 are generated at the instant t between t = 0 and t = 0.25 ms (black bar in simulation diagram on left), at different sites within the dendritic tree (schematic drawing on right). At the site of generation, these EPSPs are identical in amplitude and duration. After conduction along the dendrites, their shapes are different (theoretical recordings at the level of the soma, simulation diagram on left). It can be observed that the further away the site of generation of the EPSP (case 4), the smaller is its amplitude and the longer is its risetime (rt) when it arrives at the level of the soma (compare the theoretical recordings 1 to 4). (b) Theoretical model of the linear summation of EPSP (see text for explanation). From Rall W (1977) Handbook of Physiology, vol. 1, part 1, Bethesda, MA: American Physiological Society, with permission. From Cellular and Molecular Neurophysiology, Fourth Edition. Copyright © 2015 Elsevier Ltd. All rights reserved. 3

Figure 13.3 Non-linear summation of excitatory postsynaptic potentials. Suppose that there are two excitatory synapses situated close together on the same dendritic segment. (a) When afferent 1 is activated at time t, a depolarization of the postsynaptic membrane 1 is recorded at time t (EPSP1 alone). This depolarization propagates in the two directions away from 1. (b) When afferent 2 is activated, at time t + Δt, a depolarization of the postsynaptic membrane 2 is recorded (EPSP2 alone). (c) When the two afferents 1 and 2 are activated as before, but together, one at time t and the other at time t + Δt, a depolarization of the postsynaptic membrane 2 (ΣEPSP) is recorded at time t + Δt, which does not correspond to the geometric sum EPSP1 alone + EPSP2 alone, since EPSP2′ has an amplitude which is smaller than EPSP2 (see text for explanation). From Cellular and Molecular Neurophysiology, Fourth Edition. Copyright © 2015 Elsevier Ltd. All rights reserved. 4

Figure 13.4 Integration of excitatory (EPSP) and inhibitory (IPSP) postsynaptic potentials. (a) Suppose that on a dendritic tree, there are glutaminergic excitatory synapses which are situated distally, and GABAB-type inhibitory synapses which are situated proximally, and that all of these are active at the same instant t. (b) If only the excitatory synapses are active, a depolarization, a composite EPSP (ΣEPSP) will be recorded at the soma which corresponds to the linear and non-linear summation of all the different EPSPs (top trace). We will suppose that the ΣEPSP has an amplitude that is sufficient to trigger an action potential (upper trace). If only the inhibitory synapses are active, a hyperpolarization, a composite IPSP (ΣIPSP) will be recorded at the soma which corresponds to the linear and non-linear summation of all the different IPSPs (middle trace). When all these different synapses are activated at the same time t, a depolarization preceded by a hyperpolarization, a composite PSP, will be recorded at the soma, corresponding to the sum of the different synaptic potentials (ΣEPSP + ΣIPSP) (bottom trace). In this case, the amplitude of the depolarization is no longer sufficient to trigger an action potential. (c) Electrical equivalent of the membrane at the level of the initial segment, for an EPSP alone. (d) Electrical equivalent for the membrane when an EPSP and an IPSP summate. The currents IEPSP and IIPSP are opposite and subtract from one another. By comparing with (c), it is observed that IEPSP in (c) is greater than IEPSP + IIPSP in (d), and ΔVl > ΔV2. From Cellular and Molecular Neurophysiology, Fourth Edition. Copyright © 2015 Elsevier Ltd. All rights reserved. 5

6 Figure 13.5 Role of silent inhibition. (a) This diagram shows two synapses, one glutamatergic with postsynaptic AMPA receptors (E1) and the other GABAergic with GABAA postsynaptic receptors (I1), situated close to one another on the same dendritic segment, such that the inhibitory synapse is closer to the soma than the excitatory synapse. (b) When the excitatory synapse is excited alone, an EPSP of ΔV1 in amplitude is recorded (b1). When the inhibitory synapse is activated alone, no change in potential is recorded because Vm = ECl (b2). When both synapses are activated, the EPSP which propagates towards the soma is reduced in amplitude (amplitude ΔV3), or even cancelled out. This type of inhibition is selective because it only acts on excitatory synapses that are situated distally. (c) Electrical equivalent of the membrane at the dendritic segment. If this is compared with Figure 13.4c, it can be seen that ΔV3gm. From Cellular and Molecular Neurophysiology, Fourth Edition. Copyright © 2015 Elsevier Ltd. All rights reserved. 6