Functional clustering of dendritic activity during decision-making

Abstract

The active properties of dendrites support local nonlinear operations, but previous imaging and electrophysiological measurements have produced conflicting views regarding the prevalence of local nonlinearities in vivo. We imaged calcium signals in pyramidal cell dendrites in the motor cortex of mice performing a tactile decision task. A custom microscope allowed us to image the soma and up to 300 µm of contiguous dendrite at 15 Hz, while resolving individual spines. New analysis methods were used to estimate the frequency and spatial scales of activity in dendritic branches and spines. The majority of dendritic calcium transients were coincident with global events. However, task-associated calcium signals in dendrites and spines were compartmentalized by dendritic branching and clustered within branches over approximately 10 µm. Diverse behavior-related signals were intermingled and distributed throughout the dendritic arbor, potentially supporting a large computational repertoire and learning capacity in individual neurons.

Impact of functional synapse clusters on neuronal response selectivity

“…These observations motivated the idea of functional synaptic clustering: to elicit dendritic spikes, inputs showing correlated in vivo activity should target nearby dendritic locations (Larkum & Nevian, 2008). Consistent with this idea, in vivo imaging of the activity of dendritic spines demonstrated that neighbouring synapses are co-activated more often than random (Takahashi et al, 2012;Winnubst et al, 2015;Iacaruso et al, 2017;Scholl et al, 2017;Kerlin et al, 2018) suggesting the involvement of active processes in the formation of functional clusters. However, both the relative importance of synaptic clustering compared to other factors influencing neuronal responses under in vivo conditions and the biophysical mechanisms leading to their formation are unknown.…”

“…In particular, the spatial scale of the synapses showing correlated activity in vivo has been found to be restricted to 5-10 µm and involved a small number, ∼2-5 dendritic spines (Takahashi et al, 2012;Iacaruso et al, 2017;Scholl et al, 2017;Kerlin et al, 2018). This is substantially less than the 10-20 inputs required to trigger dendritic spikes under in vitro conditions (Mel, 1993;Losonczy & Magee, 2006;Makara & Magee, 2013;Branco & Häusser, 2011) leaving the potential impact of the clusters elusive.…”

A unifying framework for synaptic organization on cortical dendrites

“…Despite functional synaptic clustering in the developing hippocampus (1)(2)(3)8) , no such fine-scale spatial organization was initially observed in the mature sensory cortex (12)(13)(14)16) . The emerging evidence now points to species-specificity of synaptic clustering for different stimulus features (6,7,9,10) . To reconcile these findings, we developed a unifying computational framework for the emergence of both local and global synaptic input organization on cortical dendrites.…”

“…(1) The transient, precise synchronization of even a small group of synapses can result in the nonlinear summation of synaptic activity (62) , enhancing a neuron's computational capacity (18) (however, see refs. (9,63) ). These nonlinearities can counteract location-dependent gradients of conductances across synapses, effectively establishing a synaptic democracy (9,64) .…”

“…(9,63) ). These nonlinearities can counteract location-dependent gradients of conductances across synapses, effectively establishing a synaptic democracy (9,64) . (2) Since synaptic transmission is highly variable (65) , multiple synapses encoding a similar signal might compensate for the potential failure of each individual synapse, thus effectively boosting the signal to noise ratio of synaptic transmission.…”