Experience-Dependent Development of Dendritic Arbors in Mouse Visual Cortex

Abstract

The dendritic arbor of neurons constrains the pool of available synaptic partners and influences the electrical integration of synaptic currents. Despite these critical functions, our knowledge of the dendritic structure of cortical neurons during early postnatal development and how these dendritic structures are modified by visual experience is incomplete. Here, we present a large-scale dataset of 849 3D reconstructions of the basal arbor of pyramidal neurons collected across early postnatal development in visual cortex of mice of either sex. We found that the basal arbor grew substantially between postnatal day 7 (P7) and P30, undergoing a 45% increase in total length. However, the gross number of primary neurites and dendritic segments was largely determined by P7. Growth from P7 to P30 occurred primarily through extension of dendritic segments. Surprisingly, comparisons of dark-reared and typically reared mice revealed that a net gain of only 15% arbor length could be attributed to visual experience; most growth was independent of experience. To examine molecular contributions, we characterized the role of the activity-regulated small GTPase Rem2 in both arbor development and the maintenance of established basal arbors. We showed that Rem2 is an experience-dependent negative regulator of dendritic segment number during the visual critical period. Acute deletion of Rem2 reduced directionality of dendritic arbors. The data presented here establish a highly detailed, quantitative analysis of basal arbor development that we believe has high utility both in understanding circuit development as well as providing a framework for computationalists wishing to generate anatomically accurate neuronal models.

Dendritic branch structure compartmentalizes voltage-dependent calcium influx in cortical layer 2/3 pyramidal cells

“…Our experiments were conducted in juvenile mice (between P21 and P28). Although the dendritic branch structure is static after this age ( Koleske, 2013 ; Richards et al, 2020 ), it is possible that changes in channel composition dampen the effects of dendritic branch structure on excitability. We show that such effects are possible with compartment models ( Figure 7F ), and it is known that changes in dendritic excitability can occur as a result of synaptic plasticity induction ( Frick et al, 2003 ; Frick et al, 2004 ; Losonczy et al, 2008 ).…”

Emergence of synaptic organization and computation in dendrites

“…Finally, recent experimental data demonstrate that dendritic growth is affected by synaptic activity ( ), suggesting that changes to dendritic morphology might facilitate dendritic map formation. Since early development is characterized by the establishment of dendritic morphology ( ) and by repeated and rapid synapse turnover ( ; ), it appears as a particularly opportune time for the formation of dendritic maps.…”

Dendritic growth and synaptic organization from activity-independent cues and local activity-dependent plasticity

“…Despite the residual amount of expansion and retraction, we showed that morphological stability increases rapidly, and the dendrite morphology is already stable after the initial expansion phase ( Figure 2 d). Interestingly, rapid stabilization of morphology also occurs in the mouse visual cortex ( Richards et al, 2020 ) and the Drosophila larvae ( Castro et al, 2020 ). The rapid slowing down of growth in our model is not due to a depletion of potential synaptic partners as the number of potential synapses remains high ( Figure 2 e).…”

“…Here we focus on the early developmental period of highly dynamic growth and retraction. However, dendritic morphology remains remarkably stable in later development and throughout adult-hood ( Richards et al, 2020 ; Castro et al, 2020 ; Koleske, 2013 ). This stability is achieved despite substantial increases in overall size of the animal ( Richards et al, 2020 ; Castro et al, 2020 ) and ongoing functional and structural plasticity of synapses ( Kleindienst et al, 2011 ; Winnubst et al, 2015 ; Kirchner and Gjorgjieva, 2021 ).…”

“…Despite the residual amount of expansion and retraction, we showed that morphological stability increases rapidly, and the dendrite morphology is already stable after the initial expansion phase (Figure 2d). Interestingly, rapid stabilization of morphology also occurs in the mouse visual cortex (Richards et al, 2020) and the Drosophila larvae (Castro…”