Simulated responses of cerebellar Purkinje cells are independent of the dendritic location of granule cell synaptic inputs.

Abstract

Cerebellar Purkh je cell responses to granule cell synaptic inputs were examined with a computer model including active dendritic conductances. Dendritic P-type Ca2+ channels amplified postsynaptic responses when the model was firing at a physiological rate. Small synchronous excitatory inputs applied distally on the large dendritic tree resulted in somatic responses of similar size to those generated by more proximal inputs. In contrast, in a passive model the somatic postsynaptic potentials to distal inputs were 76% smaller. The model predicts that the somatic firing response of Purkinje cells is relatively insensitive to the exact dendritic location of synaptic inputs. We describe a mechanism of Ca2+-mediated synaptic amplification, based on the subspiking threshold recruitment of P-type Ca2+ channels in the dendritic branches surrounding the input site.The interaction between the geometry of a neuron's dendrite and how that neuron processes synaptic information is a central question in neurobiology. Theoretical analysis by Rall (1) and others (2) has shown that in large dendritic trees, synaptic inputs on distal locations will be attenuated much more than inputs on proximal branches before they arrive at the soma. A generally accepted conclusion from these studies is that the exact dendritic location of synaptic inputs is quite important (3). However, this analysis is based on the assumption of a passive dendritic membrane. The cerebellar Purkinje cell has a large dendritic tree (4), covered with an enormous number ofexcitatory parallel fiber synapses (5). The geometry of the cerebellar molecular layer is such that parallel fibers make synapses at similar vertical positions in all Purkinje cells they contact (4 Because increases in membrane conductance also increase the electrotonic length of dendrites, the presence of active channels on the Purkinje cell dendrite and the continuous background synaptic input from the parallel fibers could both be expected to further enhance synaptic attenuation (9-11).In this paper, we use a Purkinje cell model (11,12) to show that the active properties of the dendrite actually interact with the background synaptic input and with the passive electrical properties of the cell to amplify distal synaptic inputs, effectively negating the significance of dendritic location. Our modeling results suggest that in Purkinje cells all granule cell inputs have equal access to the soma independent of their spatial position. If correct, this result has profound implications for the nature of information processing within the cerebellar cortex. MODEL AND METHODSAll simulations used a detailed compartmental model of a Purkinje cell based on reconstructed dendritic anatomy (13). The model was simulated with GENESIS (14) and has been described in detail elsewhere (11,12 The sensitivity of the model to localized synaptic inputs was tested by giving small synchronous excitatory inputs (time to peak, 0.8 ms; 0.7 nS) on 200 spines. These spines were put on dendritic branches with a diamet...

Background Synaptic Activity Modulates the Response of a Modeled Purkinje Cell to Paired Afferent Input

“…We have previously shown, first using this model (Jaeger et al 1997) and then experimentally (Jaeger and Bower 1999), that the dendro-somatic current is responsible for regulating the spiking activity of the Purkinje cell. This current counter-balances the somatic currents when stimulated with background activity and directly drives the soma to fire when a direct stimulus is delivered (De Schutter and Bower 1994c;Jaeger and Bower 1999;Jaeger et al 1997). We have also shown that the dendritic CaP and Kca currents in the model are the most activated under this kind of stimulation while the other dendritic currents are averaged out (Santamaria et al 2002).…”

“…Ascending segment input was distributed over eight different branchlets (De Schutter and Bower 1994c;Santamaria et al 2002). Inhibitory interneuron synaptic inputs were distributed uniformly over the spiny branchlets (Fig.…”

“…Specifically, we have proposed that the large number of parallel fiber synapses made by granule cells on Purkinje cells may be responsible for controlling the dynamics of the dendrite and not for directly driving the spiking output of the cell (Jaeger and Bower 1999;Jaeger et al 1997). Previous physiological (Bower and Woolston 1983;Cohen and Yarom 1998;Jaeger and Bower 1994), anatomical (Gundappa-Sulur et al 1999), and modeling studies (De Schutter and Bower 1994c;Jaeger et al 1997;Santamaria et al 2002) suggest that the timing of Purkinje cell spiking activity is more directly under the control of synapses associated with the ascending segment of the granule cell axon. This proposed differential functionality of synapses actually associated with the same axon is based on anatomical differences in the location of synapses (Gundappa-Sulur et al 1999;Mugniani 1972), the dynamic properties of the large voltage-dependent conductances found in the Purkinje cell dendrite (Llinas and Sugimori 1980), and differences in the influences of inhibitory molecular layer interneurons on each type of input (Hausser and Clark 1997).…”

“…Although neuronal dendrites have traditionally most often been modeled as spatial and temporal summing devices (see London and Segev 1999;Rall 1999), it is clear that the presence of active conductances in dendrites substantially affects how these structures integrate synaptic inputs (Cook and Johnston 1999;De Schutter and Bower 1994c;London and Segev 2001;Poirazi et al 2003;Williams and Stuart 2002). In fact, model (Chance et al 2002)-and experimental-based (Frick et al 2004) studies of the functional consequences of active dendritic membranes are starting to raise questions about whether all synapses are fundamentally "driving" in nature.…”

Spike-Timing–Dependent Synaptic Plasticity and Synaptic Democracy in Dendrites

“…These mechanisms are able to effectively augment the efficacies of synapses, in particularly that of the distal synapses (Bernander et al 1994;De Schutter and Bower 1994) so that the efficacy of synapses is not dominated only by passive properties of the dendritic cable. In fact, calcium spikes were shown to have an important role in determining the efficacy of the STDP induction process .…”