BACKGROUND:  The concept of operant learning describes how consequences are used to modify voluntary behavior. Operant learning is often associated with training animals to encourage or modify certain actions, but it also has implications in humans. There are a variety of psychiatric disorders, movement disorders, and addictions in which operant learning is implicated. Previous studies have demonstrated biological correlations with operant learning, where dopamine is activated after a conditioned stimulus and plasticity occurs in many regions of the cortex. Methods to regulate the physiology associated with operant learning could provide new therapies for a range of conditions in which learning and behavioral functions are compromised, such as schizophrenia, Tourette's syndrome, Attention-Deficit/Hyperactivity Disorder (ADHD), and neurodegenerative diseases.

INNOVATION:  Researchers at UCLA have identified a sphingosine-1-phosphare (S1P) receptor, Gpr6, which is selectively expressed in the striatopallidal neurons in the striatum and involved in the signaling pathway associated with operant learning. Blocking this target may selectively enhance the acquisition and performance of operant learning in humans. Preventing ligands from binding to this receptor could also reduce the chances of a subject forgetting a previously established reward-outcome contingency. The investigators observed that blocking the receptor selectively enhances instrumental learning without affecting other behavioral aspects, such as Pavlovian learning and motor activity.

POTENTIAL APPLICATIONS 

• Therapeutic target provides the basis to develop compounds that facilitate the treatment of medical disorders where operant learning is part of the treatment regimen.

ADVANTAGES

• The target utilizes a previously unknown pathway that can improve operant learning activities and alleviate cognitive deficits.
• May be used in conjunction with existing therapies to improve the ability to learn action-outcome association.

DEVELOPMENT-TO-DATE:  Proof-of-concept experiments have demonstrated that Gpr6-deficient mice exhibited enhanced instrumental acquisition and performance. Therefore, Gpr6 is the first striatopallidal neuron-specific genetic regulator of instrumental conditioning in a mammal.

Related Papers (Selected)

• Genetic control of instrumental conditioning by striatopallidal neuron–specific S1P receptor Gpr6 [more...]

Reference: UCLA Case No. 2007-480