Calakos Lab

201E Bryan Research

Nicole Calakos, MD, PhD, PI


Research Office: 919-684-2423

Location: 201E Bryan

We all know that as part of our daily lives we are constantly interacting with our environment - learning, adapting, establishing new memories and habits, and for better or for worse, forgetting as well. At the cellular level, these processes can be encoded by changes in the strength of synaptic transmission between neurons. The process by which neuronal connections change in response to experience is known as “synaptic plasticity” and this process is a major interest of our laboratory. Our goals are to understand the molecular mechanisms for synaptic plasticity and identify when these processes have gone awry in neurological diseases. In doing so, we will establish the necessary framework to target these processes for therapeutic interventions; potentially identifying novel and improved treatment options.

We focus these interests on the striatal circuitry of the basal ganglia. The striatum is a key entry point for cortical information into the basal ganglia. The basal ganglia are involved in a wide variety of behaviors because they are critical for our movement, including the learning of motor routines and when to call them into action. Disorders in this process have wide ranging manifestations from Parkinson’s disease to OCD. One important aspect of basal ganglia circuit function is the balance of activity between the “direct” (striatonigral) and “indirect” (striatopallidal) pathways. Imbalance between these pathways has been implicated in diseases such as Parkinson’s and Huntington’s and is likely to contribute to others. 

To get a better view of how pathway balance may be affected, our lab has developed tools and approaches that make it possible to study the function of striatal medium spiny neurons in each of these pathways simultaneously in living tissue (Shuen et al., 2008; Ade et al., 2011, O’Hare and Ade et al., 2016). We use them to identify functional differences between these two types of medium spiny neurons and their role in normal adaptive plasticity and disease processes.

In habit, we have identified circuit predictors of behavior. These include some classic expectations for mechanisms of plasticity such as increased firing activity, but also some surprises, like finding shifts in the timing of firing between these two cell types (O’Hare and Ade et al., 2016).

In disease models, we examine the synaptic and circuit basis for repetitive, compulsive behaviors by studying the synaptic role of SAPAP3 and its relation to Obsessive Compulsive Disorder (OCD)-like behaviors in mice (Welch et al., 2007; Chen et al., 2011; Wan et al., 2011, Ade et al., 2016). One of the major outcomes of this work has been identifying a central role for striatal group 1 metabotropic glutamate receptor overactivity in driving OCD-like behaviors and brain activity in rodents (Chen et al., 2011; Wan et al., 2011, Ade et al. ,2016).

Other studies examine the role of corticostriatal transmission in the pathophysiology of movement disorders such as dystonia and Tourette’s Syndrome.

To tackle all of these research questions, we use cellular electrophysiological recording techniques and advanced imaging methods to directly evaluate neuronal activity. As we uncover the molecular and cellular basis of synaptic plasticity, we test the implications of our findings at the circuit and behavioral levels. We take advantage of a range of molecular genetic and imaging technologies to do this. Our research is also greatly influenced by the rich collaborations we have with colleagues at Duke and beyond.

Support Our Research

Recent Posts

Wednesday, September 22, 2021 - 12:00
DIBS Cube - Multi-purpose room
Elana Lockshin

PhD candidate Elana Lockshin (Calakos Lab) will present The role of the unfolded-protein-response in the dopaminergic system for proper locomotion and cognition in-person on Wed. Sept. 22 at noon.

Tuesday, May 4, 2021
By Karl Leif Bates

The discovery of a signaling pathway in the brain that could make mice into ‘superlearners’ understandably touched off a lot of excitement a few years back.

Ruan headshot
Wednesday, December 2, 2020 - 12:00
Shaolin Ruan

Second-year Neurobiology graduate student Shaolin Ruan (Calakos Lab) will present “Learning by reducing inhibition: Dorsomedial striatal somatostatin expressing interneurons regulate goal-directed learning"  an analysis of