Distinguishing linear vs. non-linear integration in CA1 radial oblique dendrites: it’s about time

Abstract

It was recently shown that multiple excitatory inputs to CA1 pyramidal neuron dendrites must be activated nearly simultaneously to generate local dendritic spikes and supralinear responses at the soma; even slight input desynchronization prevented local spike initiation (Gasparini and Magee, 2006; Losonczy and Magee, 2006). This led to the conjecture that CA1 pyramidal neurons may only express their non-linear integrative capabilities during the highly synchronized sharp waves and ripples that occur during slow wave sleep and resting/consummatory behavior, whereas during active exploration and REM sleep (theta rhythm), inadequate synchronization of excitation would lead CA1 pyramidal cells to function as essentially linear devices. Using a detailed single neuron model, we replicated the experimentally observed synchronization effect for brief inputs mimicking single synaptic release events. When synapses were driven instead by double pulses, more representative of the bursty inputs that occur in vivo, we found that the tolerance for input desynchronization was increased by more than an order of magnitude. The effect depended mainly on paired-pulse facilitation of NMDA receptor-mediated responses at Schaffer collateral synapses. Our results suggest that CA1 pyramidal cells could function as non-linear integrative units in all major hippocampal states.

Synaptic clustering within dendrites: An emerging theory of memory formation

“…In this case, synchronous stimulation of nearby synapses (mimicking functional clustering , see Figure 1) had the same effect as synchronous stimulation of the same number of synapses distributed uniformly within the branch ( in-branch localization ), suggesting that these structures act as single, nonlinear integrative compartments, as predicted by previous modeling work (Poirazi et al, 2003a, 2003b). These dendrites have also been suggested to act as coincidence detectors (Ariav et al, 2003; Gómez González, Mel, & Poirazi, 2011; Losonczy & Magee, 2006) and serve as detectors of asynchronous bursty inputs (Gómez González et al, 2011), via the induction of fast or slow, respectively, dendritic spikes. Evidence of such independent integrative compartments provides support for a 2-stage model of neuronal processing (Katz et al, 2009; Poirazi et al, 2003b), with multiple implications with respect to information processing (for a recent review on the 2-layer model, see (M.…”

Spine Head Calcium as a Measure of Summed Postsynaptic Activity for Driving Synaptic Plasticity

“…However, as has been demonstrated for the generation of PC spiking output (Gómez González, Mel, & Poirazi, 2011;Poirazi, Brannon, & Mel, 2003a, 2003b, spatial localization of synaptic input also has a significant effect on pCa levels. Inputs restricted to a single dendritic branch show a much higher gain in pCa level as a function of the number of active inputs, compared to distributed synapses.…”

Computer modeling of hippocampal CA1 pyramidal cells - a tool for in silico experiments

“…The authors originally studied the linear and non-linear synaptic integration, but being a very detailed model, it was suitable to study dendritic integration by several other authors, e.g. the thin dendritic branches as a separate integration level of the synaptic inputs, with sigmoidal summation of the neighboring inputs [52], the influence of synchronization and different spatial distribution of synaptic inputs on the proximal and distal dendrites on the information content of the neuronal response [53], complex (non-linear) as opposed to a passive (linear) information processing [54], the distance-dependent synaptic scaling [55], depolarization block [56]. This model was also used to study the alterations of the CA1 pyramidal cells in different pathological conditions, e.g.…”