Local Glutamate-Mediated Dendritic Plateau Potentials Change the State of the Cortical Pyramidal Neuron

Abstract

37Dendritic spikes in thin dendritic branches (basal and oblique dendrites) of pyramidal neurons 38 are traditionally inferred from spikelets measured in the cell body. Here, we used laser-spot 39 voltage-sensitive dye imaging in cortical pyramidal neurons (rat brain slices) to investigate the 40 voltage waveforms of dendritic potentials occurring in response to spatially-restricted 41 glutamatergic inputs. Local dendritic potentials lasted 200-500 ms and propagated to the cell 42 body where they caused sustained 10-20 mV depolarizations. Plateau potentials propagating 43 from dendrite to soma, and action potentials propagating from soma to dendrite, created 44 complex voltage waveforms in the middle of the thin basal dendrite, comprised of local sodium 45 spikelets, local plateau potentials, and back-propagating action potentials, superimposed on 46 each other. Our model replicated these experimental observations and made the following 47 predictions: (i) membrane time constant is shortened during the plateau; and (ii) synaptic 48 responses are more effective drivers of neuronal action potentials during the plateau potential.49 Dendritic plateau potentials occurring in basal and oblique branches put pyramidal neurons into 50 an activated neuronal state ("prepared state"), characterized by depolarized membrane potential 51 and notably faster membrane responses. The prepared state provides a time window of 200-52 500 ms during which cortical neurons are particularly excitable and capable of following afferent 53 inputs. At the network level, this predicts that sets of cells with simultaneous plateaus would 54 provide cellular substrate for the formation of functional neuronal ensembles. 55 56 57 58 59Significance statement: Strong and clustered glutamatergic inputs will have a major 60 influence on activity at both neuronal and network scales. We recorded glutamate-mediated 61 dendritic voltage plateaus using voltage imaging, and created a computer model that recreated 62 experimental measures. Our model predicts the manner in which plateaus are triggered and the 63 impact of inputs to an individual thin dendrite on the membrane response in the cell body. 64 Plateau potentials profoundly change neuronal state --a plateau potential triggered in one basal 65 dendrite depolarizes the soma and shortens membrane time constant, making the cell more 66 susceptible to firing triggered by other afferent inputs. We tested model predictions 67 experimentally. 68 69 70 The individual spiny neuron is subjected to a variety of excitatory input patterns, often resulting 71 from concurrent release across multiple synapses on a single dendrite. Due to combinations of 72 temporal and spatial clustering 1-3 , the amount of glutamate released on a single basilar dendrite 73 can be quite large, potentially spilling over to extrasynaptic NMDA receptors, and temporarily 74 overwhelming the ability of astrocytes to fully compensate. In vitro focal applications of 75 comparable amounts of glutamate, or repetitive synaptic stimulations, wi...

Effects of Ihand TASK-like shunting current on dendritic impedance in layer 5 pyramidal-tract neurons

“…These changes preserved the perisomatic firing characteristics of the original model and fit experimental data from PT cells in primary motor cortex while also reproducing additional I h -dependent phenomena observed experimentally [16, 19, 54, 68]. More detailed information regarding the parameters and properties of the models studied here may be found in their original publications [16, 18, 23, 38, 54].…”

“…The density of Ca 2 + channels was increased near the nexus of the apical tufts forming a “hot-zone” [23]. Model 2 was based on data from frontal cortex of Sprague-Dawley rats, P21-33, fit using voltage-sensitive dye imaging data with a focus on reproducing dendritic plateau potentials and their propagation toward the soma, dendritic sodium spikelets, and backpropagating action potentials in the basal dendrites [1, 18]. The distribution of I h channels was constant in the basal dendrites and increased exponentially with distance from the soma in the apical dendrites.…”

“…The relatively high expression of HCN in PTs endows them with resonance, giving the properties of a band-pass filter [13, 30, 75]. We here report that five previously developed, biophysically-detailed multi-compartment models of neocortical PTs exhibit dendrite-location-dependent impedance profiles with resonant frequencies and synchronous frequencies increasing with distance from the soma [16, 18, 23, 38, 54]. Four of the five models have resonant frequencies in line with experimental findings, ranging from 4-9 Hz [13, 75], while the fifth produced resonant frequencies above this range.…”

Deficits in integrative NMDA receptors caused byGrin1disruption can be rescued in adulthood

“…This integrative phenomenon depends on the recruitment of extrasynaptic NMDARs ( Fig 3A ), and would be vulnerable if this population were compromised ( Fig 3B ). Dendritic plateau potentials are considered an important cognitive substrate to link multiple streams of incoming information and generate burst firing 16,19,20,31 , an output signal predicted to exert stronger downstream consequences 32,33 . Deficient extrasynaptic NMDARs are predicted to have profound consequences for such signaling 7,28 .…”

“…Such temporal and spatial integration is required to generate dendritic plateau potentials 2,7,18,19 . These NMDAR-mediated integration events trigger burst firing 7,19 , a robust neuronal response 32,33 , thought to be essential for behaviour-evoked network activity 4,20,43 . Our results indicate that developmental disorders with reduced NMDARs are likely to have compromised neurophysiological integration resulting from disrupted extrasynaptic NMDAR population.…”