M1-selective allosteric modulation enhances cognitive flexibility

We have new research out at PNAS about enhancing cognitive flexibility with highly selective allosteric modulation of the M1 muscarinic receptor (pdf: here)!

Muscarinic receptors are known to mediate pro-cognitive effects of acetylcholine, but it has remained unclear whether they differentially affect the cognitive subfunctions of attentional filtering, set shifting, and learning. To clarify the functional specificity of M1 mAChRs, we assessed these diverse functions using a recently developed, highly selective M1 PAM developped at the Warren Center of Neuroscience Drug Discovery by co-authors Prof. Jones and Dr. Russel. This novel M1 PAM caused domain-specific cognitive improvement of flexible learning and extradimensional set shifting, reduced perseverations and enhanced target recognition during learning without altering attentional filtering functions. These domain-specific improvements contrasted to effects of a nonselective acetylcholinesterase inhibitor that primarily enhanced attention and caused dose-limiting adverse side effects. These results demonstrate domain-specific improvements in cognitive flexibility suggesting M1 PAMs are versatile compounds for treating cognitive deficits in schizophrenia and Alzheimer’s disease.

Related News

Striatum interneurons track learning of attention cues

Our new paper shows how fast spiking interneurons in the striatum activate specifically when attention cues are learned. This is a rare paper where we succeed to isolate fast spiking interneurons in recordings from nonhuman primate anterior striatum while the animals performed a complex feature-based attentional learning task. Phd can. Kia Banaeie Boroujeni spearheaded the […]

New Multi-task cognitive profiling platform for NHPs+humans

We published a new unity based software platform for profiling cognitive and motivational constructs in nonhuman primates and humans. The platform has multiple pre-configured tasks with some gamified features that makes them engaging to play for participants. Details are described and linked on the website: http://m-use.psy.vanderbilt.edu. The technical details are available in Watson et al. […]

Effective Connectivity Shows Asymmetries in Resonance and Latencies between Medial and Lateral Prefrontal Cortex Connections

The lab has a first article published about the strength, latency and resonance patterns of connections between the anterior cingulate cortex and lateral prefrontal cortex of the macaque. This work was led by postdoc Veronica Nacher and is published in Brain Structure and Function. The paper identifies a novel electrical microstimulation protocol that can be […]