Cell Type- and Subcellular Position-Dependent Summation of Unitary Postsynaptic Potentials in Neocortical Neurons

Abstract

Theoretical studies predict that the modes of integration of coincident inputs depend on their location and timing. To test these models experimentally, we simultaneously recorded from three neocortical neurons in vitro and investigated the effect of the subcellular position of two convergent inputs on the response summation in the common postsynaptic cell. When scattered over the somatodendritic surface, combination of two coincident excitatory or inhibitory synaptic potentials summed linearly in layer 2/3 pyramidal cells, as well as in GABAergic interneurons. Slightly sublinear summation with connection specific kinetics was observed when convergent inputs targeted closely placed sites on the postsynaptic cell. The degree of linearity of summation also depended on the type of connection, the relative timing of inputs, and the activation state of I h . The results suggest that, when few inputs are active, the majority of afferent permutations undergo linear integration, maintaining the importance of individual inputs. However, compartment-and connection-specific nonlinear interactions between synapses located close to each other could increase the computational power of individual neurons in a cell typespecific manner. Key words: cerebral cortex; integration; IPSP; EPSP; interneuron; pyramidal cellThe rules of synaptic summation are thought to depend on the dendritic geometry of the postsynaptic cell (Zador et al., 1995;Mainen et al., 1996), on a variety of synaptic-and voltagedependent conductances distributed heterogeneously over the dendritic tree (Johnston et al., 1996;Hausser et al., 2000), and on the relative position and timing of inputs (Jack et al., 1975;Shepherd and Brayton, 1987;Rall et al., 1992;Segev et al., 1995;Hausser et al., 2000). Theoretical analysis of dendritic integration began by assuming that passive cables serve as reasonable models of dendrites (Jack et al., 1975;Segev et al., 1995). According to cable theory, electrically isolated inputs sum linearly, whereas closely located inputs produce an attenuated response as a consequence of reduction in the ionic driving force or a decrease in dendritic input resistance leading to shunting of synaptic currents (Jack et al., 1975;Segev et al., 1995). However, dendritic membranes are not passive, because they contain voltage-dependent conductances, which could selectively amplify distal inputs or subserve local nonlinear operations (Koch et al., 1983;Mel, 1993). Direct experimental determination of the influence of the location of synaptic inputs on dendritic integration has been relatively sparse. Electrophysiological analysis in vivo showed sublinear summation in motoneurons (Kuno and Miyahara, 1969) and both linear and nonlinear modes of integration of responses in the visual system (Douglas et al., 1988;Jagadeesh et al., 1993Jagadeesh et al., , 1997Borggraham et al., 1998;Hirsch et al., 1998;Kogo and Ariel, 1999;Anderson et al., 2000). Experiments in brain slices indicated linear input summation in motoneurons (Skydsgaard and Hounsgaard, 199...

Dendritic spines linearize the summation of excitatory potentials

“…Although we have only explored basal spines at particular distances (most of them at 20-80 m) from the soma, the locations of the examined spines cover the regions of highest spine density in pyramidal neurons (34,41), and basal dendrites can host the majority of the spines of pyramidal cells (42). With respect to other cell types besides mouse layer 5 neurons, linear or near-linear summation of EPSPs has been also documented in rat hippocampal pyramidal neurons (22,23), rat neocortical layer 2/3 and layer 5 cells in vitro (24,27) and in vivo (25), and even rat Purkinje cells in vitro (43). Because all of these neurons share spine-laden dendrites, we would extend our interpretation to spiny cells more generally, proposing that the reason these neurons integrate linearly is precisely because their inputs are mediated by spines.…”

“…39). In addition, linear summation of EPSPs (presumably activating spines) has been found in CA1 (23) and neocortical pyramidal neurons in vitro (24,27) and in vivo (25).…”

“…In addition, neocortical neurons integrate excitatory inputs linearly in vitro (24) and in vivo (25). Summation experiments using one-photon uncaging of glutamate or extracellular stimulation on neocortical pyramidal neurons have confirmed that excitatory inputs as close as 40 m can sum linearly, although closer stimulation, or stimulation with stronger currents, generated local spikes (26)(27)(28).…”

Roller Coaster Scanning reveals spontaneous triggering of dendritic spikes in CA1 interneurons

“…Although thoroughly investigated in principal cells, the occurrence of these events in interneurons has not been shown, despite the major role interneurons play in oscillations and pattern generation (1). Because previous studies dealt with interneurons as global, single-layer integrator units consisting of linearly, slightly sublinearly integrating dendrites, faithful postsynaptic information relay by a single AP initiation zone was assumed (9,33,34). The present study shows that clustered input patterns can produce strongly supralinear dendritic integration in RAD INs even though they have more simple, aspiny dendrites.…”

“…Spatial clustering of synchronized synaptic inputs can lead to nonlinear integration and regenerative events in dendrites of principal neurons, increasing their computational power (2)(3)(4)(5)(6)(7)(8). On the contrary, interneurons were previously suggested to have more linear or sublinear integration propertiesfeatures that might imply a passive involvement in neuronal operations (9). Dendritic integration in principal cells is mediated by multiple layers of logical integrators (2,6,10), the first layer being the apical Ca 2+ and axonal Na + integration zone, generating relatively more global propagating spikes.…”