Circuit-Specific Dendritic Development in the Piriform Cortex

Abstract

Dendritic geometry is largely determined during postnatal development and has a substantial impact on neural function. In sensory processing, postnatal development of the dendritic tree is affected by two dominant circuit motifs, ascending sensory feedforward inputs and descending and local recurrent connections. In the three-layered anterior piriform cortex (aPCx), neurons in the sublayers 2a and 2b display vertical segregation of these two circuit motifs. Here, we combined electrophysiology, detailed morphometry, and Ca 21 imaging in acute mouse brain slices and modeling to study circuit-specific aspects of dendritic development. We observed that determination of branching complexity, dendritic length increases, and pruning occurred in distinct developmental phases. Layer 2a and layer 2b neurons displayed developmental phase-specific differences between their apical and basal dendritic trees related to differences in circuit incorporation. We further identified functional candidate mechanisms for circuit-specific differences in postnatal dendritic growth in sublayers 2a and 2b at the mesoscale and microscale levels. Already in the first postnatal week, functional connectivity of layer 2a and layer 2b neurons during early spontaneous network activity scales with differences in basal dendritic growth. During the early critical period of sensory plasticity in the piriform cortex, our data are consistent with a model that proposes a role for dendritic NMDA-spikes in selecting branches for survival during developmental pruning in apical dendrites. The different stages of the morphologic and functional developmental pattern differences between layer 2a and layer 2b neurons demonstrate the complex interplay between dendritic development and circuit specificity.

Plasticity of olfactory bulb inputs mediated by dendritic NMDA-spikes in rodent piriform cortex

“…To get more insight with regard to the potential feasibility of NMDA-spikes to occur in vivo, we estimated the probability of their occurrence under in vivo-like conditions based on the following assumptions from the literature: (1) typically layer IIb pyramidal neurons (PNs) in adult mice have 10 terminal apical branches ( Moreno-Velasquez et al, 2020 ). (2) The size of the LOT band is ~100 µm ( Bekkers and Suzuki, 2013 ; Moreno-Velasquez et al, 2020 ).…”

“…To get more insight with regard to the potential feasibility of NMDA-spikes to occur in vivo, we estimated the probability of their occurrence under in vivo-like conditions based on the following assumptions from the literature: (1) typically layer IIb pyramidal neurons (PNs) in adult mice have 10 terminal apical branches ( Moreno-Velasquez et al, 2020 ). (2) The size of the LOT band is ~100 µm ( Bekkers and Suzuki, 2013 ; Moreno-Velasquez et al, 2020 ). (3) Typical number of spine density is at least 1 spine/µm, which would result in at least ~100 spines per single-terminal branch at the LOT band.…”

“…This band is almost exclusively innervated by LOT axons ( Bekkers and Suzuki, 2013 ; Giessel and Datta, 2014 ; Kumar et al, 2018 ). Thus, per terminal branch there are ample of LOT synapses given that ~10 synapses are needed to initiate a local NMDA-spike ( Antic et al, 2010 ; Major et al, 2013 ; Moreno-Velasquez et al, 2020 ; Polsky et al, 2009 ). However, a critical question relates to the statistics of LOT activation during a natural odor stimulation.…”

“… Srinivasan and Stevens, 2018 estimated that each piriform neuron randomly receives ~0.64 synapses from each single glomerulus. Assuming 110 glomeruli are activated by a typical odor yields activation of 70 LOT synapses per neuron ( Moreno-Velasquez et al, 2020 ; Srinivasan and Stevens, 2018 ). Further, assuming random independent connectivity of LOT inputs to layer IIb PNs ( Giessel and Datta, 2014 ; Moreno-Velasquez et al, 2020 ) and random distribution of LOT synapses over the terminal branches, we calculated the probability that at least one terminal dendritic branch will be simultaneously activated by 10 or more random LOT synapses (the estimated number for NMDA-spike initiation) in any given neuron to be 15% ( Figure 3—figure supplement 2 ).…”

“…2. The size of the LOT band is ~ 100 microns (Bekkers and Suzuki, 2013;Moreno-Velasquez et al, 2020). 3.…”