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High-resolution and cell-type-specific photostimulation mapping shows weak excitatory vs. strong inhibitory inputs in the bed nucleus of the stria terminalis.
J Neurophysiol 2016; 115(6):3204-16JN

Abstract

The bed nucleus of the stria terminalis (BNST) is a key component of the extended amygdala and has been implicated in anxiety and addiction. As individual neurons function within neural circuits, it is important to understand local microcircuits and larger network connections of identified neuronal types and understand how maladaptive changes in the BNST neural networks are induced by stress and drug abuse. However, due to limitations of classic anatomical and physiological methods, the local circuit organization of synaptic inputs to specific BNST neuron types is not well understood. In this study, we report on the application of high-resolution and cell-type-specific photostimulation methodology developed in our laboratory to local circuit mapping in the BNST. Under calibrated experimental conditions, laser photostimulation via glutamate uncaging or channelrhodopsin-2 photoactivation evokes spiking of BNST neurons perisomatically, without activating spikes from axons of passage or distal dendrites. Whole cell recordings, combined with spatially restricted photostimulation of presynaptic neurons at many different locations over a large region, allow high-resolution mapping of presynaptic input sources to single recorded neurons in the BNST. We constructed maps of synaptic inputs impinging onto corticotrophin-releasing hormone-expressing (CRH+) BNST neurons in the dorsolateral BNST and found that the CRH+ neurons receive predominant local inhibitory synaptic connections with very weak excitatory connections. Through cell-type-specific optogenetic stimulation mapping, we generated maps of somatostatin-expressing neuron-specific inhibitory inputs to BNST neurons. Taken together, the photostimulation-based techniques offer us powerful tools for determining the functional organization of local circuits of specific BNST neuron types.

Authors+Show Affiliations

Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, California; Department of Biomedical Engineering, University of California, Irvine, California; Department of Microbiology and Molecular Genetics, University of California, Irvine, California; xiangmin.xu@uci.edu.Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, California;Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, California;Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, California;Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, California;Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, California; and.Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27052587

Citation

Xu, Xiangmin, et al. "High-resolution and Cell-type-specific Photostimulation Mapping Shows Weak Excitatory Vs. Strong Inhibitory Inputs in the Bed Nucleus of the Stria Terminalis." Journal of Neurophysiology, vol. 115, no. 6, 2016, pp. 3204-16.
Xu X, Ikrar T, Sun Y, et al. High-resolution and cell-type-specific photostimulation mapping shows weak excitatory vs. strong inhibitory inputs in the bed nucleus of the stria terminalis. J Neurophysiol. 2016;115(6):3204-16.
Xu, X., Ikrar, T., Sun, Y., Santos, R., Holmes, T. C., Francesconi, W., & Berton, F. (2016). High-resolution and cell-type-specific photostimulation mapping shows weak excitatory vs. strong inhibitory inputs in the bed nucleus of the stria terminalis. Journal of Neurophysiology, 115(6), pp. 3204-16. doi:10.1152/jn.01148.2015.
Xu X, et al. High-resolution and Cell-type-specific Photostimulation Mapping Shows Weak Excitatory Vs. Strong Inhibitory Inputs in the Bed Nucleus of the Stria Terminalis. J Neurophysiol. 2016 06 1;115(6):3204-16. PubMed PMID: 27052587.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-resolution and cell-type-specific photostimulation mapping shows weak excitatory vs. strong inhibitory inputs in the bed nucleus of the stria terminalis. AU - Xu,Xiangmin, AU - Ikrar,Taruna, AU - Sun,Yanjun, AU - Santos,Rommel, AU - Holmes,Todd C, AU - Francesconi,Walter, AU - Berton,Fulvia, Y1 - 2016/04/06/ PY - 2015/12/27/received PY - 2016/04/04/accepted PY - 2016/4/8/entrez PY - 2016/4/8/pubmed PY - 2017/9/8/medline KW - GABAergic KW - extended amygdala KW - glutamate uncaging KW - glutamatergic KW - optogenetic stimulation KW - synaptic connections SP - 3204 EP - 16 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 115 IS - 6 N2 - The bed nucleus of the stria terminalis (BNST) is a key component of the extended amygdala and has been implicated in anxiety and addiction. As individual neurons function within neural circuits, it is important to understand local microcircuits and larger network connections of identified neuronal types and understand how maladaptive changes in the BNST neural networks are induced by stress and drug abuse. However, due to limitations of classic anatomical and physiological methods, the local circuit organization of synaptic inputs to specific BNST neuron types is not well understood. In this study, we report on the application of high-resolution and cell-type-specific photostimulation methodology developed in our laboratory to local circuit mapping in the BNST. Under calibrated experimental conditions, laser photostimulation via glutamate uncaging or channelrhodopsin-2 photoactivation evokes spiking of BNST neurons perisomatically, without activating spikes from axons of passage or distal dendrites. Whole cell recordings, combined with spatially restricted photostimulation of presynaptic neurons at many different locations over a large region, allow high-resolution mapping of presynaptic input sources to single recorded neurons in the BNST. We constructed maps of synaptic inputs impinging onto corticotrophin-releasing hormone-expressing (CRH+) BNST neurons in the dorsolateral BNST and found that the CRH+ neurons receive predominant local inhibitory synaptic connections with very weak excitatory connections. Through cell-type-specific optogenetic stimulation mapping, we generated maps of somatostatin-expressing neuron-specific inhibitory inputs to BNST neurons. Taken together, the photostimulation-based techniques offer us powerful tools for determining the functional organization of local circuits of specific BNST neuron types. SN - 1522-1598 UR - https://www.unboundmedicine.com/medline/citation/27052587/High_resolution_and_cell_type_specific_photostimulation_mapping_shows_weak_excitatory_vs__strong_inhibitory_inputs_in_the_bed_nucleus_of_the_stria_terminalis_ L2 - http://www.physiology.org/doi/full/10.1152/jn.01148.2015?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -