| Summary: | Different types of local inhibitory interneurons innervate different dendritic sites of pyramidal neurons in cortex and hippocampus (Klausberger 2009). What could be the functional role of compartmentalized inhibition? <br/> <br/>Pyramidal cell dendrites support different forms of active signal propagation, which are important not only for dendritic and neuronal signal processing (Smith et al. 2013), but also for synaptic plasticity. While back-propagating action potentials signal post-synaptic activity to synapses in apical oblique and basal dendrites (Markram et al. 1997, Cho et al. 2006), calcium spikes cause plasticity of distal apical tuft synapses (Golding et al. 2002). Suspiciously, the associated regions of the dendrite are targeted by different interneuron populations. Parvalbumin-positive interneurons typically target the proximal dendritic and somatic parts of the neuron, while somatostatin-positive interneurons target the apical dendrite. The matching compartmentalization in terms of dendritic spikes and inhibitory control suggests that inhibition could differentially regulate different dendritic spikes and thereby introduce a compartment-specific modulation of synaptic plasticity. <br/> <br/>We evaluate this hypothesis in a biophysical multi-compartment model of a pyramidal neuron, receiving shunting inhibition at different locations on the dendrite. The model shows that, first, inhibition can gate dendritic spikes in an all-or-none manner. Second, spatially selective inhibition can individually suppress back-propagating action potentials and calcium spikes, thereby allowing a compartment-specific switch for synaptic plasticity. In our model, proximal inhibition on the apical dendrite eliminated both the back-propagating action potential and the calcium spike, thus influencing plasticity in the whole apical dendrite. Distal apical inhibition could selectively affect calcium spikes and thus distal plasticity, without suppressing backpropagation of action potentials into apical obliques and the basal dendrites. Proximal basal inhibition could prevent backpropagation into the basal dendrites, without preventing dendritic spikes in the apical dendrite. A quantitative investigation of these observations showed that the modulation of calcium spikes is rather insensitive to timing while inhibition of the fast back-propagating action potential required precisely timed inhibition within a window of 1ms of the initiation of the somatic action potential. Third, when inhibition was on the path between driving input and spike initiation zone, two different scenarios need to be distinguished. Either, the driving input is passively propagated to the soma, in which case modulation of the back-propagating action potential occurs under similar conditions as for somatic stimulation. Alternatively, if synaptic stimulation triggers dendritic spikes, back-propagation is impaired, abolishing the possibility of inhibitory modulation of the back-propagating action potential. <br/> <br/>Because different excitatory synaptic pathways converge onto distinct dendritic compartments, the proposed mechanism could implement a pathway-specific switch for synaptic plasticity, a potentially useful feature for learning and the formation of memories.
|
|---|
