Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior
From biting fingernails to the daily commute, habits can be completed almost without thinking and are difficult to change or stop. Behavioral neuroscientists refer to habits as “stimulus-response” behaviors, and know that forming a new habit requires a region deep within the brain called the dorsolateral striatum. In this region, the outgoing neurons – which make up 95% of the cells - respond differently to incoming signals in mice that have learned habits compared to non-habitual mice. However a question remained: what exactly was producing these differences? Calakos and team have now found, unexpectedly, that the answer resides not in the 95% of outgoing neurons, but rather in a rare type of cell known as the fast-spiking interneuron.
O'Hare, J., Li, H., Kim, N., Gaidis, E., Ade, K., Beck, J., Yin, H., Calakos, N. Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior. eLife 2017;6:e26231 doi: 10.7554/eLife.26231.
Cocaine dependence modulates the effect of HIV infection on brain activation during intertemporal decision making
Both HIV infection and chronic cocaine use alter the neural circuitry of decision making, but the interactive effects of these commonly comorbid conditions have not been adequately examined. This study tested how cocaine moderates HIV-related neural activation during an intertemporal decision-making task.
Meade, C., Hobkirk, A., Towe, S., Chen, N., Bell, R., Huettel, S. Cocaine dependence modulates the effect of HIV infection on brain activation during intertemporal decision making. Drug and Alcohol Dependence(178): 443-451, 1 Sept. 2017.
Altered neurogenesis and disrupted expression of synaptic proteins in prefrontal cortex of SHANK3-deficient non-human primate
Mutations in SHANK3 gene is one of the best replicated autism causing genes in human. We reported the first non-human primate autism model for SHANK3 causing autism using CRISPR/Cas9 technique. The finding from neuropathological study of SHANK3 mutant monkey provide a unique insight to understand the pathophysiology of autism in human.
Zhao, H., Tu, Z., Xu, H., Yan, S., Yan, H., Zheng, Y., Yang, W., Zheng, J., Li, Z., Tian, R., Lu, Y., Guo, X., Jiang, Y., and Zhang, Y.Q. Altered neurogenesis and disrupted expression of synaptic proteins in prefrontal cortex of SHANK3-deficient non-human primate. Cell Research, 25 July 2017.
Learning to speak is thought to require pathways that transmit motor-related signals to auditory regions of the brain. Despite their postulated importance to vocal learning, the identity of such motor to sensory (i.e., forward) pathways has remained unknown, and their role in vocal learning is largely untested. Roberts, Hisey et al describe a motor to auditory pathway in the songbird brain that is important to juvenile song imitation and adult modification of vocal timing, providing evidence of forward pathways important to vocal learning.
Roberts, Todd F, Hisey, Erin, Tanaka, Masashi, Kearney, Matthew G., Gattree, Gaurav, Yang, Cindy f., Shah, Nirao M., & Mooney, Richard. Identification of a motor-to-auditory pathway important for vocal learning. Nature Neuroscience, 15 May 2017.
SHANK3, expressed by peripheral primary sensory neurons, regulates TRPV1 function and heat hyperalgesia after inflammation and nerve injury, and therefore offers a mechanistic insight into pain dysregulation in autism.
Han Q, Kim YH, Wang X, Liu D, Zhang ZJ, Bey AL, Lay M, Chang W, Berta T, Zhang Y, Jiang YH, and Ji RR. SHANK3 deficiency impairs heat hyperalgesia and TRPV1 signaling in primary sensory neurons. Neuron, 1 December 2016.
Capturing and manipulating activated neuronal ensembles with CANE delineates a hypothalamic social-fear circuit
In its debut performance, a powerful new genetic engineering tool has revealed secrets of functionally distinct brain circuits for social fear and aggression in mice. This, even though these sets of neurons seem hopelessly intertwined. The tool, called CANE (Capturing Activated Neuronal Ensembles), helps trace distinct pathways embedded within the brain's spaghetti-like wiring.
Sakurai K, Zhao S, Takatoh J, Rodriquez E, Lu, J, Leavitt AD, Fu M, Han B-X, Wang F. Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit, Neuron, Vol. 92, Issue 4, 23 November 2016, 739-753.
Molecular Tool Parses Social Fear Circuit Intertwined with Aggression Hub
Manipulating neurons in an activity-dependent manner
In this review, we discuss how pain can be regulated by non-neuronal cells such as glial cells and immune cells via interactions with nociceptive neurons. We also discuss new therapeutic strategies to control neuroinflammation for the prevention and treatment of chronic pain.
Ji RR, Chamessian A, Zhang YQ. Pain Regulation by Non-neuronal Cells and Inflammation. Science, 2016, November 4, 354, 572-577.
Synapses can change the magnitude of their future responses based upon their past experience. This is called plasticity and is thought to be essential to learning and memory. In this paper, we characterize a critical signaling pathway that regulates the process of plasticity. Furthermore, we provide direct evidence of the site of action of this signaling pathway, which has been controversial in the field.
Harward, S. C., Hedrick, N. G., Hall, C. E., Parra-bueno, P., Milner, T. A., Pan, E., … Yasuda, R., McNamara J.O. (2016). Autocrine BDNF-TrkB signalling within a single dendritic spine, 13–16. doi:10.1038/nature19766
Neurons in the brain encode information obtained from the outside world as well as our own internal state. This information is transferred between neurons through the release of neurotransmitters at synapses. Each neuron can receive input from thousands of other neurons. In this paper, we demonstrate a signaling mechanism that allows a neuron to bind information received over a defined time window at nearby synapses. This mechanism could form the foundation of a basic neural computation.
Hedrick, N. G., Harward, S. C., Hall, C. E., Murakoshi, H., McNamara, J. O., & Yasuda, R. (2016). Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity. Nature. doi:10.1038/nature19784
Inhibitory synapses act as the brakes in the brain, preventing it from becoming overexcited. Researchers thought they were less sophisticated than their excitatory counterparts because relatively few proteins were known to exist at these structures. But a new study by the Soderling Lab, published Sept. 9 in Science, overturns that assumption, uncovering 140 proteins that have never been mapped to inhibitory synapses. “It’s like these proteins were locked away in a safe for over 50 years, and we believe that our study has cracked open the safe,” said the study’s senior investigator Scott Soderling, an Associate Professor of Cell Biology and Neurobiology at Duke. “And there’s a lot of gems.” In particular, 27 of these proteins have already been implicated by genome studies as having a role in autism, intellectual disability and epilepsy, Soderling said, suggesting that their mechanisms at the synapse could provide new avenues to the understanding and treatment of these disorders.
Akiyoshi Uezu, Daniel J. Kanak, Tyler W.A. Bradshaw, Eric Soderblom, Christina M. Catavero, Alain C. Burette, Richard Weinberg, Scott H. Soderling. Identification of an elaborate complex mediating postsynaptic inhibition. Science, 2016 September 9, 353, 1123-1129.
A Peptide Uncoupling BDNF Receptor TrkB from Phospholipase Cγ1 Prevents Epilepsy Induced by Status Epilepticus
Lack of preventive therapies for common disorders of the nervous system constitutes a major unmet medical need. Here we report a novel strategy targeting receptor tyrosine kinase signaling and identify a therapeutic for prevention of temporal lobe epilepsy.
Gu, B., Huang, Yang Zhong Huang, He, Xiao-Ping He, Joshi, R. B., Jang, Wonjo, & McNamara, J.O. A Peptide Uncoupling BDNF Receptor TrkB from Phospholipase Cγ1 Prevents Epilepsy Induced by Status Epilepticus. Neuron 88(3):484-491, 2015. PMID:26481038. PMCID: pending