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

Abstract

Santamaria, Fidel and James M. Bower. Background synaptic activity modulates the response of a modeled Purkinje cell to paired afferent input. J Neurophysiol 93: [237][238][239][240][241][242][243][244][245][246][247][248][249][250] 2005. First published August 11, 2004; doi:10.1152/jn.00458.2004. We studied the possible effects of background excitatory and inhibitory synaptic activity on Purkinje cell responses to paired pulse inputs using a morphologically and physiologically detailed compartmental model. Paired-pulse inputs were provided via synapses associated with the ascending segment of the granule cell axon in the presence of variable amounts of background synaptic input provided by parallel fibers and inhibitory interneurons. The results predict the amplitude and dynamics of the somatic and dendritic responses to paired ascending segment inputs are modulated by the level of background synaptic activity, the basal somatic firing rate of the Purkinje cell model does not indicate the type or degree of modulation, and the modulatory effects are mediated through dendritic calcium and calcium-activated potassium currents. These results have important consequences for the functional organization of cerebellar cortex as well as the more general issue of the modulatory as distinct from driving effects of synapses now also being considered in other regions of the mammalian brain including the cerebral cortex. I N T R O D U C T I O NIn recent years, there has been a continually growing interest in the interaction between the active electrical properties of neuronal dendrites and the responses of those dendrites to synaptic input (Chance et al. 2002;Euler and Denk 2001;Hausser and Mel 2003;Migliore and Shepherd 2002). 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. Specifically, it is now being suggested that some synapses might be more involved in regulating dendritic dynamics than in directly influencing the spiking output of neurons (Chance et al. 2002;De Schutter and Bower 1994b;Jaeger and Bower 1999;Jaeger et al. 1997;Rhodes and Llinas 2001;Santamaria et al. 2002;Sherman and Guillery 1998).The cerebellar Purkinje cell was one of the first mammalian neurons in which experimental studies demonstrated substantial voltage-dependent dendritic conductances (Llinas and Sugimori 1980). Using an articulated set of modeling and experimental studies, we have engaged in a series of experiments intended to better understand the f...

The functional architecture of the shark's dorsal-octavolateral nucleus:an in vitro study

“…Alternative models, according to which parallel fibers adjust the response properties of the Purkinje-like AENs, have been suggested (Paulin, 2005;Paulin and Nelson, 1993;Paulin et al, 1998). These alternative models are consistent with experimental evidence (Bastian, 1986;Bower, 2002;Santamaria and Bower, 2005) about neuronal interactions in cerebellum and cerebellar-like sensory filtering structures.…”

Correlations Between Purkinje Cell Single-Unit Activity and Simultaneously Recorded Field Potentials in the Immediately Underlying Granule Cell Layer

“…A previous in vitro study has shown that a single activation of ascending granule cell synapses can, in fact, produce prolonged intracellular plateau potentials in PCs (Jaeger and Bower 1994). Subsequent modeling studies (Santamaria and Bower 2005;Santamaria et al 2002) have suggested that these prolonged changes in PC activity are attributable to the long time constants of the calcium-related voltage-dependent conductances found in the dendrite and soma of PCs (Llinas and Sugimori 1980a,b). Interestingly, our models also suggest that the duration of these prolonged responses may be modulated by the rate of parallel fiber input to the PC dendrite (Santamaria and Bower 2005;Santamaria et al 2002).…”

“…However, these authors quantified evoked activity using an indirect voltage-sensitive dye measure in a slice preparation in which GABAergic inhibitory mechanisms were suppressed. We have recently shown that inhibition plays an important role in regulating the response of PCs to both ascending and parallel fiber granule cell inputs (Santamaria and Bower 2005;Santamaria et al 2002). In the absence of GABA inhibition, the slice preparation used by Vranesic et al (1994) in combination with direct electrical stimulation is likely to have artificially overwhelmed any effect of the ascending branch synapses.…”

“…Subsequent modeling studies (Santamaria and Bower 2005;Santamaria et al 2002) have suggested that these prolonged changes in PC activity are attributable to the long time constants of the calcium-related voltage-dependent conductances found in the dendrite and soma of PCs (Llinas and Sugimori 1980a,b). Interestingly, our models also suggest that the duration of these prolonged responses may be modulated by the rate of parallel fiber input to the PC dendrite (Santamaria and Bower 2005;Santamaria et al 2002). Such an influence might account for differences seen here between spontaneous and evoked activity in pairs with prolonged correlations.…”

“…Correlations between Purkinje cell single-unit activity and simultaneously recorded field potentials in the immediately underlying granule cell layer. J Neurophysiol 94: 1849 -1860, 2005. First published May 31, 2005 doi:10.1152/jn.01275.2004.…”