Local glutamate-mediated dendritic plateau potentials change the state of the cortical pyramidal neuron

Abstract

Dendritic spikes in thin dendritic branches (basal and oblique dendrites) are traditionally inferred from spikelets measured in the cell body. Here, we used laser-spot voltage-sensitive dye imaging in cortical pyramidal neurons (rat brain slices) to investigate the voltage waveforms of dendritic potentials occurring in response to spatially-restricted glutamatergic inputs. Local dendritic potentials lasted 200-500 ms and propagated to the cell body, where they caused sustained 10-20 mV depolarizations. Plateau potentials propagating from dendrite to soma, and action potentials propagating from soma to dendrite, created complex voltage waveforms in the middle of the thin basal dendrite, comprised of local sodium spikelets, local plateau potentials, and back-propagating action potentials, superimposed on each other. Our model replicated these voltage waveforms across a gradient of glutamatergic stimulation intensities. Model then predicted that somatic input resistance (Rin) and membrane time constant (TAU) may reduce during dendritic plateau potential. We then tested these model predictions in real neurons, and found that model correctly predicted the direction of Rin and TAU change, but not the magnitude. In summary, dendritic plateau potentials occurring in basal and oblique branches put pyramidal neurons into an activated neuronal state ("prepared state"), characterized by depolarized membrane potential, and smaller, but faster membrane responses. The prepared state provides a time window of 200-500 ms during which cortical neurons are particularly excitable and capable of following afferent inputs. At the network level, this predicts that sets of cells with simultaneous plateaus would provide cellular substrate for the formation of functional neuronal ensembles.

Studying Synaptically Evoked Cortical Responses ex vivo With Combination of a Single Neuron Recording (Whole-Cell) and Population Voltage Imaging (Genetically Encoded Voltage Indicator)

“…The hyperpolarizing potentials have a very small amplitude (in the range of only −5 mV) and they are localized to a small fraction of the neuronal surface (perisomatic membrane mostly). On the contrary, depolarizing signals, such as glutamate-mediated dendritic spikes, may achieve ∼50 mV amplitude in dendritic branches ( Gao et al, 2021 ), and these depolarizing signals may occur in any dendritic branch, across the entire dendritic tree of any pyramidal neuron ( Oikonomou et al, 2014 ). Large amplitude depolarizations in dendrites combined with large active membrane area contained in dendritic branches, allow the depolarizing signals to dominate over the hyperpolarizing population responses (small amplitude and restricted to perisomatic membranes) ( Isaacson and Scanziani, 2011 ).…”

Synapse-specific diversity of distinct postsynaptic GluN2 subtypes defines transmission strength in spinal lamina I

“…Since its discovery in cortical pyramidal cell dendrites over 20 years ago 53 the NMDAR spike continues to receive considerable focus in different cortical regions [54][55][56][57][58] . Notably, recent evidence has uncovered critical features of NMDAR-containing synapses that contribute to the generation of spikes including synapse number 59 , proximity to other synapses 59 , spatial clustering [60][61][62] , as well as their dendritic location [63][64][65] . Given our findings here, we propose for consideration the potential role GluN2 synaptic diversity and organization may impose on dendritic spike threshold and efficacy in firing in neurons in which NMDAR spikes predominate.…”

Avoiding Catastrophe: Active Dendrites Enable Multi-Task Learning in Dynamic Environments

“…When input to an active dendritic segment reaches a threshold, the segment initiates a dendritic spike (Antic et al, 2010). In basal dendritic segments, dendritic spikes travel to the cell body and can depolarize the neuron for an extended period of time, sometimes as long as half a second (Antic et al, 2010;Major et al, 2013;Gao et al, 2021). During this time, the cell is significantly closer to its firing threshold and any new input is more likely to make the cell fire.…”