Differential dendritic integration of long-range inputs in association cortex via subcellular changes in synaptic AMPA-to-NMDA receptor ratio

A dendritic mechanism for balancing synaptic flexibility and stability

“…After early visual experience, dLGN-recipient dendrites of L5 PNs lose NMDAR-mediated properties, creating an entire dendritic domain with linearly-integrating synapses that are unable to potentiate. Our findings align with a recent study in adult association cortex which also observed linearly integrating oblique dendrites (Lafourcade et al, 2022). Together, these findings demonstrate that NMDAR-mediated integration is not universal within the dendritic tree of adult cortical neurons, in contrast to prior theories (Larkum et al 2009).…”

“…However, higher-order cortical representations remain highly plastic (Makino and Komiyama, 2015; Pakan et al, 2018; Poort et al, 2015; Weskelblatt and Niell, 2019). Because single cortical neurons receive spatially-targeted inputs (Lafourcade et al, 2022; Morgenstern et al, 2016; Petreanu et al, 2009; Young et al, 2021), we hypothesized that dendritic compartmentalization could arbitrate plasticity or stability for different kinds of information. Using glutamate uncaging, focal stimulation, and super-resolution microscopy, we identified dLGN-recipient and nonrecipient dendritic domains within layer 5 pyramidal neurons (PNs) and tracked the synaptic properties and plasticity of these domains across maturation.…”

Cell-type-specific integration of feedforward and feedback synaptic inputs in the posterior parietal cortex

“…By contrast, RS neurons displayed similar integration profiles regardless of input combination. Nonlinear dendritic processes are most powerful when synaptic inputs are arranged within a branch, not separated by a bifurcation point (Polsky et al, 2004), and can vary across individual branches (Harnett et al, 2013;Lafourcade et al, 2022). One possible explanation for cell-type-specific afferent interactions is that auditory and visual afferents target distinct dendritic branches in IB cells, preventing cross-modal interactions.…”

Probing Action Potential Generation and Timing under Multiplexed Basal Dendritic Computations Using Two-photon 3D Holographic Uncaging

“…The input-output relationship across these thin basal dendrites follows the well accepted two-layer-model of computation (Jadi et al, 2014; Poirazi et al, 2003) with a stark location-dependence (Behabadi et al, 2012). Here, synchronously activated inputs result in a sigmoidal input-output transformation when clustered, a linear to sub-linear relationship when distributed (Branco and Häusser, 2011; Major et al, 2008), exhibit a NMDAR dependence (Branco and Häusser, 2011; Hill et al, 2013; Lafourcade et al, 2022; Major et al, 2008; Schiller et al, 2000), and play a crucial role in axo-somatic integration (Antic et al, 2010; Major et al, 2013). .…”

“…AODs on the other hand, offer higher positioning speeds but suffer from spatio-temporal distortion of ultrafast laser pulses, and exhibit a wavelength-dependent low diffraction efficiency leading to small field of views, precluding 3D uncaging to date (Losavio et al, 2009). Two-photon uncaging of transmitters using a set of galvanometers allows for precise stimulation of individual and synaptic clusters respectively (Branco and Häusser, 2011; Harnett et al, 2012; Lafourcade et al, 2022; Losonczy et al, 2008; Weber et al, 2016). Galvanometric mirrors can be programmed to allow for fast beam steering and rapid repositioning (∼ 100 μ s) with little to no power loss, however, they are limited to a single focal plane and cannot assay three-dimensional synaptic distributions (Gasparini et al, 2004).…”