Genetic identity of thermosensory relay neurons in the lateral parabrachial nucleus.
The parabrachial nucleus is important for thermoregulation because it relays skin temperature information from the spinal cord to the hypothalamus. Prior work in rats localized thermosensory relay neurons to its lateral subdivision (LPB), but the genetic and neurochemical identity of these neurons remains unknown. To determine the identity of LPB thermosensory neurons, we exposed mice to a warm (36°C) or cool (4°C) ambient temperature. Each condition activated neurons in distinct LPB subregions that receive input from the spinal cord. Most c-Fos+ neurons in these LPB subregions expressed the transcription factor marker FoxP2. Consistent with prior evidence that LPB thermosensory relay neurons are glutamatergic, all FoxP2+ neurons in these subregions colocalized with green fluorescent protein (GFP) in reporter mice for Vglut2, but not for Vgat. Prodynorphin (Pdyn)-expressing neurons were identified using a GFP reporter mouse and formed a caudal subset of LPB FoxP2+ neurons, primarily in the dorsal lateral subnucleus (PBdL). Warm exposure activated many FoxP2+ neurons within PBdL. Half of the c-Fos+ neurons in PBdL were Pdyn+, and most of these project into the preoptic area. Cool exposure activated a separate FoxP2+ cluster of neurons in the far-rostral LPB, which we named the rostral-to-external lateral subnucleus (PBreL). These findings improve our understanding of LPB organization and reveal that Pdyn-IRES-Cre mice provide genetic access to warm-activated, FoxP2+ glutamatergic neurons in PBdL, many of which project to the hypothalamus.
Department of Neurology, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts; jgeerlin@bidmc.harvard.edu.
Joel C
JC
Geerling
Department of Neurology, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts;
Minjee
M
Kim
Department of Neurology, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts;
Carrie E
CE
Mahoney
Department of Neurology, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts;
Stephen B G
SB
Abbott
Department of Neurology, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts;
Lindsay J
LJ
Agostinelli
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts; Centre for Integrative Physiology, University of Edinburgh, Edinburgh, Scotland;
Alastair S
AS
Garfield
Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; and National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland.
Michael J
MJ
Krashes
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts;
Bradford B
BB
Lowell
Department of Neurology, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, Massachusetts;
Thomas E
TE
Scammell
D000818:Animals; D004195:Disease Models, Animal; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D005334:Fever / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005838:Genotype; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007035:Hypothermia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D000067556:Internal Ribosome Entry Sites; D008297:Male; D008822:Mice, Transgenic; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000378:metabolism*; D065823:Parabrachial Nucleus / Q000378:metabolism* / Q000503:physiopathology; D010641:Phenotype; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012881:Skin Temperature; D013697:Thermosensing; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
D004745:Enkephalins; D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; D000067556:Internal Ribosome Entry Sites; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012097:Repressor Proteins; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; C033660:preproenkephalin; C045073:Cre recombinase; D019426:Integrases