Sparse innervation and local heterogeneity in the vibrissal corticostriatal projection

Reviewer #1 (Public review):

Summary:

By applying a laser scanning photostimulation (LSPS) approach to a novel slice preparation, the authors aimed to study the degree of convergence and divergence of cortical inputs to individual striatal projection neurons (SPNs).

Strengths:

The experiments were well-designed and conducted, and data analysis was thorough. The manuscript was well written, and related work in the literature was properly discussed. This work has the potential to advance our understanding of how sensory inputs are integrated into the striatal circuits.

Weaknesses:

This work focuses on the connection strength of the corticostriatal projections, without considering the involvement of synaptic plasticity in sensory integration.

Reviewer #2 (Public review):

Summary:

How corticostriatal synaptic connectivity gives rise to SPN encoding of sensory information is an important and currently unanswered question. The authors utilize a clever slice preparation in combination with electrophysiology and glutamate uncaging to dissect the synaptic connectivity between barrel cortex and individual striatal SPNs. In addition to mapping connectivity across major anatomical axes and cortical layers, the authors provide data showing that SPNs uniquely integrate sparse input from variable stretches across barrel cortex.

Strengths:

The methodology shows impressive rigor, and the data robustly support the authors' conclusions. Overall, the manuscript addresses its core question, provides valuable insights into corticostriatal architecture, and is a welcome addition to the field.

Weaknesses:

A few minor changes to the figures and text could be made to improve clarity.

Reviewer #3 (Public review):

Summary:

The authors explored how individual dorsolateral striatum (DLS) spiny projection neurons (SPNs) receive functional input from whisker-related cortical columns. The authors developed and validated a novel slice preparation and method to which they applied rigorous functional mapping and thorough analysis. They found that individual SPNs were driven by sparse, scattered cortical clusters. Interestingly, while the cortical input fields of nearby SPNs had some degree of overlap, connectivity per SPN was largely distinct. Despite sparse, heterogeneous connectivity, topographical organization was identified. The authors lastly compared direct (D1) vs. indirect (D2) pathway cells, concluding that overall connectivity patterns were the same, but D1 cells received stronger input from L6 and D2 cells from L2/3. The paper thoughtfully addresses the question of whether barrel cortex broadly or selectively innervates SPNs. Their results indicate selective input that is loosely topographic. Their work deepens the understanding of how whisker-related somatosensory signals can drive striatal neurons.

Strengths:

Overall, this is a carefully conducted study, and the major claims are well-supported. The use of a novel ex vivo slice prep that keeps relevant corticostriatal projections intact allows for careful mapping of the barrel cortex to dorsolateral striatum SPNs. Careful reporting of both columnar and layer position, as well as postsynaptic SPN type (D1 or D2), allows the authors to uncover novel details about how the dorsolateral striatum represents whisker-related sensory information.

Weaknesses:

(1) Several factors may contribute to an underestimation of barrel cortex inputs to SPNs (and thus an overestimate of the input heterogeneity among SPNs). First, by virtue of the experiments being performed in an acute slice prep, it is probable that portions of recorded SPN dendritic trees have been dissected (in an operationally consistent anatomical orientation). If afferents happen to systematically target the rostral/caudal projections of SPN dendritic fields, these inputs could be missed. Similarly, the dendritic locations of presynaptic cortical inputs remain unknown (e.g., do some inputs preferentially target distal vs proximal dendritic positions?). As synaptic connectivity was inferred from somatic recordings, it's likely that inputs targeting the proximal dendritic arbor are the ones most efficiently detected. Mapping the dendritic organization of synapses is beyond the scope of this work, but these points could be broached in the text.

(2) In general, how specific (or generalizable) is the observed SPN-specific convergence of cortical barrel cortex projections in the dorsolateral striatum? In other words, does a similar cortical stimulation protocol targeted to a non-barrel sensory (or motor) cortex region produce similar SPN-specific innervation patterns in the dorsolateral striatum?

(3) In general, some of the figure legends are extremely brief, making many details difficult to infer. Similarly, some statistical analyses were either not carried out or not consistently reported.