Scientists have long viewed the primary cilium as a specialized signaling hub for G protein‑coupled receptors (GPCRs), but with a catch: ciliary GPCR activity was thought to be largely confined to non‑canonical, locally restricted cAMP pathways. Our new preprint challenges that assumption.

We reveal that, in striatal medium spiny neurons, the primary cilium is a major initiation site for endogenous D1 dopamine receptor signaling through the canonical cAMP → PKA cascade. Dopamine arriving from axon varicosities activates D1 receptors concentrated in the cilium, triggering cAMP production and PKA activation that propagate far beyond the ciliary compartment into the surrounding cytoplasm.

Strikingly, the cilium doesn’t just host the first step of this pathway, it spatially organizes the entire signaling axis, aligning dopaminergic inputs with ciliary D1 receptors and positioning downstream PKA machinery in close somatic proximity. In this system, the cilium acts not as a restrictive microdomain but as an architectural facilitator of long‑range neurotransmission.

Together, these findings expand the concept of ciliary neurotransmission and uncover a previously unappreciated role for the primary cilium in shaping dopaminergic signaling in the striatum.

https://www.biorxiv.org/content/10.64898/2026.10.05.756873v1

We are thrilled to announce that the Ehrlich Lab has received an R01 award from the National Institute on Drug Abuse (NIDA) to study the organization and regulation of the mu opioid receptor (MOR) in neurons with a focus on the primary cilium.

This research will investigate how MOR trafficking and spatial organization shape opioid receptor signaling, with the goal of uncovering fundamental mechanisms that regulate opioid neuromodulation.

This award marks an exciting milestone as we launch the Ehrlich Lab at VCU, and we are incredibly grateful to NIDA for supporting our research. We look forward to getting started!

Read about it here https://news.vcu.edu/article/vcus-aliza-ehrlich-receives-3-million-to-study-link-between-opioids-and-unexplored-neuron-structure