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.
Highlights
In vitro and modeling studies of both CA1 and neocortical pyramidal neurons have shown that the thin basal and apical branches of these cells are capable of generating local dendritic spikes (Schiller et al, 2000; Larkum et al, 2001, 2009; Wei et al, 2001; Ariav et al, 2003; Gasparini et al, 2004; Jarsky et al, 2005; Milojkovic et al, 2005; Nevian et al, 2007; Major et al, 2008), and that the voltagedependent currents that underlie dendritic spiking can lead to supralinear summation of two or more spatially convergent excitatory inputs (Shepherd and Brayton, 1987; Mel, 1993; Mel et al, 1998; Ariav et al, 2003; Poirazi et al, 2003a,b; Polsky et al, 2004; Losonczy and Magee, 2006; Katz et al, 2009)
It has been shown that multiple excitatory inputs to apical dendrites in CA1 stratum radiatum (SR) can trigger a local dendritic spike, and summate supralinearly, only when the inputs are activated nearly simultaneously (Losonczy and Magee, 2006)
It has been suggested that the dendritic integration in CA1 may be behavioral-statedependent: linear during REM sleep and awake exploration, when synchronization of CA3 inputs on a millisecond time scale is unlikely, and non-linear during the highly synchronized sharp waves and ripples associated with awake resting states and/or slow wave sleep
Summary
In vitro and modeling studies of both CA1 and neocortical pyramidal neurons have shown that the thin basal and apical branches of these cells are capable of generating local dendritic spikes (Schiller et al, 2000; Larkum et al, 2001, 2009; Wei et al, 2001; Ariav et al, 2003; Gasparini et al, 2004; Jarsky et al, 2005; Milojkovic et al, 2005; Nevian et al, 2007; Major et al, 2008), and that the voltagedependent currents that underlie dendritic spiking can lead to supralinear summation of two or more spatially convergent excitatory inputs (Shepherd and Brayton, 1987; Mel, 1993; Mel et al, 1998; Ariav et al, 2003; Poirazi et al, 2003a,b; Polsky et al, 2004; Losonczy and Magee, 2006; Katz et al, 2009). Losonczy and Magee (2006) used multi-site two-photon glutamate uncaging to stimulate varying numbers of spines on radial oblique dendrites of CA1 pyramidal neurons, with the goal to map out the spatio-temporal requirements for triggering local spikes in these branches. Magee and colleagues proposed that this very narrow window of opportunity for spike generation in oblique dendrites could allow CA1 neurons to respond selectively – or at least differently – to the highly synchronized inputs that occur during hippocampal sharp waves and high-frequency ripples as opposed to the more loosely synchronized inputs riding on theta waves (Gasparini and Magee, 2006; Losonczy and Magee, 2006) This hypothesis is important, since it points to a concrete biophysical mechanism for distinguishing between two major hippocampal states at the level of CA1 dendrites. The hypothesis makes the interesting and somewhat unintuitive prediction that when an animal is actively involved in exploring its environment and engaged in hippocampus-dependent navigation or episodic memory tasks, the principal neurons of the CA1 region are functioning as essentially linear devices (see Cash and Yuste, 1999)
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