Abstract
In vivo, cortical pyramidal cells are bombarded by asynchronous synaptic input arising from ongoing network activity. However, little is known about how such ‘background’ synaptic input interacts with nonlinear dendritic mechanisms. We have modified an existing model of a layer 5 (L5) pyramidal cell to explore how dendritic integration in the apical dendritic tuft could be altered by the levels of network activity observed in vivo. Here we show that asynchronous background excitatory input increases neuronal gain and extends both temporal and spatial integration of stimulus-evoked synaptic input onto the dendritic tuft. Addition of fast and slow inhibitory synaptic conductances, with properties similar to those from dendritic targeting interneurons, that provided a ‘balanced’ background configuration, partially counteracted these effects, suggesting that inhibition can tune spatio-temporal integration in the tuft. Excitatory background input lowered the threshold for NMDA receptor-mediated dendritic spikes, extended their duration and increased the probability of additional regenerative events occurring in neighbouring branches. These effects were also observed in a passive model where all the non-synaptic voltage-gated conductances were removed. Our results show that glutamate-bound NMDA receptors arising from ongoing network activity can provide a powerful spatially distributed nonlinear dendritic conductance. This may enable L5 pyramidal cells to change their integrative properties as a function of local network activity, potentially allowing both clustered and spatially distributed synaptic inputs to be integrated over extended timescales.
Highlights
Pyramidal cells are the principal excitatory neurons in the cerebral cortex and those in layer 5 (L5) form its primary output [1,2,3]
While the effect of this background input on the integration properties of neurons has been studied in the cell body region, little is known about how asynchronous background activity affects integration in distal dendrites, which contain nonlinear mechanisms that boost and dampen synaptic input
Our simulations, using a model of a cortical L5 pyramidal cell, show that the nonlinear NMDA receptor conductance activated by distributed background activity could increase the gain of the dendrite, enabling synaptic inputs to be integrated more effectively over the dendritic tree and over longer time intervals than previously thought possible
Summary
Pyramidal cells are the principal excitatory neurons in the cerebral cortex and those in layer 5 (L5) form its primary output [1,2,3]. A substantial fraction of the long range thalamic and cortico-cortical inputs form synapses onto the highly branched apical tuft in L1 and L2 [6,7], which is electrically remote from the soma [8]. The tuft receives many different types of signals including information on different sensory modalities, motor control and emotional state [5,9,10]. These inputs are likely to span a wide range of temporal scales, ranging from precisely timed millisecond bursts to more sustained ratecoded signals. This raises the question as to how an individual tufted L5 pyramidal cell combines and transforms such temporally and spatially diverse signals
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