Unbelievably, June is here, which means we have a bountiful crop of must-read neural circuit papers from May. Below, I’ve listed those that stood out based on relevance to the Inscopix community. The first two in the list used Inscopix technology and present results with clinical significance for neurodegenerative motor disorders. There are also excellent tour-de-force studies from the Tye lab and Anderson lab that relate to observational learning, and aggression that results from social isolation. I’ve included a little summary with each paper, and links to the original paper plus any science communication that came out on the study. Happy reading!
1. Diametric neural ensemble dynamics in parkinsonian and dyskinetic states by Jones G. Parker, Jesse D. Marshall, Biafra Ahanonu, Yu-Wei Wu, Tony Hyun Kim, Benjamin F. Grewe, Yanping Zhang, Jin Zhong Li, Jun B. Ding, Michael D. Ehlers & Mark J. Schnitzer. Nature
In this exciting paper with clinical significance, they used the Inscopix nVista calcium imaging system to uncover the neural dynamics in the indirect and direct striatal pathways that are present during parkinsonian behavioral states in the mouse 6-OHDA model. They saw striking spatial patterns in the neural activity that support the rate-model hypothesis. By giving the parkinsonian mice L-DOPA and imaging in the striatum, they revealed that parkinsonian and dyskinetic states produce opposing patterns of neural ensemble activity. Dr. Mike Ehlers explained the significance this way, “The striatal circuits of motor control are critical for disease states such as Parkinson’s disease, and restoration of neural ensemble function holds great potential as a circuit endophenotype for therapeutic development.”
2. The Striatum Organizes 3D Behavior via Moment-to-Moment Action Selection by Jeffrey E. Markowitz, Winthrop F. Gillis, Celia C. Beron, Shay Q. Neufeld, Keiramarie Robertson, Neha D. Bhagat, Ralph E. Peterson, Emalee Peterson, Minsuk Hyun, Scott W. Linderman, Bernardo L. Sabatini, Sandeep Robert Datta. Cell.
They filmed three-dimensional movements and used machine learning to parse the movements into patterns lasting only a few hundred milliseconds apiece called “syllables.” They used Inscopix nVista imaging in the dorsolateral striatum to observe neural activity during natural movements. They found that every time mice switched behaviors, the activity of indirect and direct striatal pathways increased.
When they looked at syllables, however, they found that the balance of activity between the two pathways differed. For some syllables, the direct pathway dominated; for others, the indirect pathway did. By imaging during natural behavior, they observed ensembles of neurons that displayed regular and predictable patterns of activity during particular syllables.
Finally, they induced lesions in the striatum and saw while mice were able to display all the separate syllables seen in normal mice, they failed to sequence these movements correctly rendering the animals incapable of reaching the arena’s opposite side to avoid the scent of a predator. The findings could help inform new treatments for movement disorders.
3. A midline thalamic circuit determines reactions to visual threat by Lindsey D. Salay, Nao Ishiko & Andrew D. Huberman. Nature.
When ventral midline thalamus (vMT) neurons are activated before, or during, stimuli that simulate predator threats, mice shift from saliency-reducing behaviors, like freezing, to saliency-enhancing reactions to those threats. Whereas looms typically induce freezing, activation of the vMT or the vMT→medial prefrontal cortex pathway induced tail rattling—a behaviour associated with aggression. This has implications for understanding disorders of arousal and adaptive decision-making, such as phobias, post-traumatic stress and addictions.