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neurotrophin growth factors have significant effects on the development and maintenance of the mammalian somatosensory system. Studies of transgenic mice that overexpress neurotrophins NGF and neurotrophin 3 (NT-3) at high levels in skin have shown increased sensory neuron number and enhanced innervation of specific sensory ending types. The effects of two other members of this family, BDNF and NT-4, on sensory neuron development are less clear. This study examined the role of brain-derived neurotrophic factor (BDNF) using transgenic mice that overexpress BDNF in epithelial target tissues of sensory neurons. BDNF transgenic mice had an increase in peripheral innervation density and showed selective effects on neuron survival. Neuron number in trigeminal ganglia, DRG, and SCG were unchanged, although a 38% increase in neurons comprising the placode-derived nodose–petrosal complex occurred. BDNF transgenic skin showed notable enhancement of innervation to hair follicles as detected by PGP9.5 immunolabeling. In nonhairy plantar skin, Meissner corpuscle sensory endings were larger, and the number of Merkel cells with associated innervation was increased. In trigeminal ganglia, neurons expressing trkB receptor were increased threefold, whereas trkA-positive neurons doubled. Analysis of trkB by Northern, reverse transcription-PCR, and Western assays indicated a modest increase in the expression of the T1 truncated receptor and preferential distribution to the periphery. 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1993, Expression of mRNAs for neurotrophin receptors in the dorsal root ganglion and spinal cord during development and following peripheral or central axotomy., Mol Brain Res, 17, 217, 10.1016\u002F0169-328X(93)90005-A",{"doi":834},"10.1016\u002F0169-328X(93)90005-A",{"id":24,"text":836,"url":24,"identifiers":837},"10.1038\u002F368147a0",{"doi":836},{"id":24,"text":839,"url":24,"identifiers":840},"10.1016\u002FS0896-6273(00)80542-5",{"doi":839},{"id":24,"text":842,"url":24,"identifiers":843},"10.1523\u002FJNEUROSCI.15-02-01044.1995",{"doi":842},{"id":24,"text":845,"url":24,"identifiers":846},"10.1111\u002Fj.1460-9568.1997.tb01515.x",{"doi":845},{"id":24,"text":848,"url":24,"identifiers":849},"10.1016\u002F0092-8674(94)90377-8",{"doi":848},{"id":24,"text":851,"url":24,"identifiers":852},"10.1016\u002F0092-8674(90)90476-U",{"doi":851},{"id":24,"text":854,"url":24,"identifiers":855},"Klein, 1990, Expression of the tyrosine kinase receptor gene trkB is confined to the murine embryonic and adult nervous system., Development, 109, 845, 10.1242\u002Fdev.109.4.845",{"doi":856},"10.1242\u002Fdev.109.4.845",{"id":24,"text":858,"url":24,"identifiers":859},"10.1523\u002FJNEUROSCI.17-23-09113.1997",{"doi":858},{"id":24,"text":861,"url":24,"identifiers":862},"10.1002\u002Fneu.480251212",{"doi":861},{"id":24,"text":864,"url":24,"identifiers":865},"10.1126\u002Fscience.2321006",{"doi":864},{"id":24,"text":867,"url":24,"identifiers":868},"10.1128\u002FMCB.11.1.143",{"doi":867},{"id":24,"text":870,"url":24,"identifiers":871},"10.1016\u002F0012-1606(89)90130-9",{"doi":870},{"id":24,"text":873,"url":24,"identifiers":874},"10.1111\u002F1523-1747.ep12606183",{"doi":873},{"id":24,"text":876,"url":24,"identifiers":877},"10.1002\u002Fjnr.490410113",{"doi":876},{"id":24,"text":879,"url":24,"identifiers":880},"10.1016\u002F0165-1838(87)90153-6",{"doi":879},{"id":24,"text":882,"url":24,"identifiers":883},"Ninkina, 1996, Expression and function of TrkB variants in developing sensory neurons., EMBO J, 15, 6385, 10.1002\u002Fj.1460-2075.1996.tb01029.x",{"doi":884},"10.1002\u002Fj.1460-2075.1996.tb01029.x",{"id":24,"text":886,"url":24,"identifiers":887},"Nurse, 1988, Development of Merkel cell populations with contrasting sensitivities to neonatal deafferentation in the rat whisker pad., Somatosens Mot Res, 6, 141, 10.3109\u002F08990228809144671",{"doi":888},"10.3109\u002F08990228809144671",{"id":24,"text":890,"url":24,"identifiers":891},"10.1146\u002Fannurev.ne.14.030191.002321",{"doi":890},{"id":24,"text":893,"url":24,"identifiers":894},"10.1007\u002Fs004410050933",{"doi":893},{"id":24,"text":896,"url":24,"identifiers":897},"Perl E (1992) Function of dorsal root ganglion neurons: an overview. in Sensory neurons: diversity, development, and plasticity, ed Scott SA (Oxford UP, New York), pp 3–23.",{},{"id":24,"text":899,"url":24,"identifiers":900},"Reichardt LF Farinas I (1997) Neurotrophic factors and their receptors: roles in neuronal development and function. in Molecular approaches to neural development, eds Cowan MW Jessell TM Zipurski L (Oxford UP, New York), pp 220–263.",{"doi":901},"10.1093\u002Facprof:oso\u002F9780195111668.003.0006",{"id":24,"text":903,"url":24,"identifiers":904},"10.1006\u002Fdbio.1998.8861",{"doi":903},{"id":24,"text":906,"url":24,"identifiers":907},"10.1006\u002Fmcne.1996.0011",{"doi":906},{"id":24,"text":909,"url":24,"identifiers":910},"10.1016\u002F0896-6273(90)90107-Q",{"doi":909},{"id":24,"text":912,"url":24,"identifiers":913},"10.1002\u002Fcne.902630305",{"doi":912},{"id":24,"text":915,"url":24,"identifiers":916},"10.1016\u002F0896-6273(92)90183-E",{"doi":915},{"id":24,"text":918,"url":24,"identifiers":919},"10.1111\u002Fj.1460-9568.1997.tb01372.x",{"doi":918},{"id":24,"text":921,"url":24,"identifiers":922},"10.1016\u002F0006-8993(94)91556-3",{"doi":921},{"id":24,"text":924,"url":24,"identifiers":925},"10.1016\u002F0092-8674(94)90048-5",{"doi":924},{"id":24,"text":927,"url":24,"identifiers":928},"10.1101\u002Fgad.5.5.714",{"doi":927},{"id":24,"text":930,"url":24,"identifiers":931},"10.1002\u002F(SICI)1097-0029(19960701)34:4\u003C351::AID-JEMT6>3.0.CO;2-R",{"doi":930},{"id":24,"text":933,"url":24,"identifiers":934},"10.1073\u002Fpnas.94.1.219",{"doi":933},{"id":24,"text":936,"url":24,"identifiers":937},"10.1016\u002F0197-4580(93)90112-O",{"doi":936},{"id":24,"text":939,"url":24,"identifiers":940},"10.1002\u002F(SICI)1096-9861(19980222)391:4\u003C407::AID-CNE1>3.0.CO;2-4",{"doi":939},{"id":24,"text":942,"url":24,"identifiers":943},"Wheeler, 1998, Neurotrophin receptor expression is induced in a subpopulation of trigeminal neurons that label by retrograde transport of NGF or fluoro- gold following tooth injury., Brain Res Mol Brain Res, 61, 23, 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sensory neurons that are primarily nociceptors can be divided neurochemically into two populations: isolectin B\u003Cjats:sub>4\u003C\u002Fjats:sub>(IB\u003Cjats:sub>4\u003C\u002Fjats:sub>)-positive nonpeptidergic neurons, and IB\u003Cjats:sub>4\u003C\u002Fjats:sub>-negative peptidergic neurons. It has been shown that IB\u003Cjats:sub>4\u003C\u002Fjats:sub>-positive neurons depend on glial-derived neurotrophic factor (GDNF), whereas IB\u003Cjats:sub>4\u003C\u002Fjats:sub>-negative neurons depend on NGF for survival during postnatal development (Molliver et al., 1997). Furthermore, these two populations of nociceptors terminate in distinct regions of the superficial spinal cord. To date, however, no evidence exists that indicates whether these two groups of nociceptors have distinct functional roles in the process of nociception (Snider and McMahon, 1998). To search for functional differences, we performed whole-cell voltage and current-clamp recordings on acutely isolated adult mouse dorsal root ganglion neurons that were labeled with fluorescent IB\u003Cjats:sub>4\u003C\u002Fjats:sub>. We found that IB\u003Cjats:sub>4\u003C\u002Fjats:sub>-positive neurons have longer-duration action potentials, higher densities of TTX-resistant sodium currents, and smaller noxious heat-activated currents than IB\u003Cjats:sub>4\u003C\u002Fjats:sub>-negative neurons. Furthermore, we show that NGF, but not GDNF, directly increases the number of neurons that respond to noxious heat. The different electrophysiological properties expressed by IB\u003Cjats:sub>4\u003C\u002Fjats:sub>-positive and -negative small neurons, including their different heat sensitivities, indicates that they may relay distinct aspects of noxious stimuli both acutely and after injury\u003Cjats:italic>in vivo\u003C\u002Fjats:italic>.\u003C\u002Fjats:p>",{"EN":970},"Isolectin B\u003Csub>4\u003C\u002Fsub>-Positive and -Negative Nociceptors Are Functionally Distinct",{"VOID":972},"10414978",{"VOID":974},"10.1523\u002Fjneurosci.19-15-06497.1999","2024-09-04T23:57:26.608+00:00",[126],"https:\u002F\u002Fwww.jneurosci.org\u002Flookup\u002Fdoi\u002F10.1523\u002FJNEUROSCI.19-15-06497.1999",[979,1000],{"id":980,"sortIndex":200,"researcher":24,"roles":981,"affiliations":982,"properties":993},"3718cda3-45ed-4ffb-8604-898ec2e0bf6f",[],[983],{"id":984,"sortIndex":25,"affiliation":985,"properties":24},"66e2203d-6db8-4055-bf3d-4c272efa22b1",{"id":986,"createTime":987,"updateTime":987,"relativeEntities":988,"slug":989,"properties":990,"entityType":45,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"b4666216-beed-49db-a8ac-8879886b85ce","2024-09-04T23:57:26.634+00:00",[],"Department-of-Neuroscience-Max-Delbr%C3%BCck-Center-for-Molecular-Medicine-Berlin-Buch-D-13122-Germany-",{"title":991},{"EN":992},"Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Berlin-Buch D-13122, Germany.",{"openalex":994,"orcid":996,"title":998},{"VOID":995},"A5020338160",{"VOID":997},"https:\u002F\u002Forcid.org\u002F0000-0002-2890-6352",{"EN":999},"Gary R. 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1995, Variation in serotonergic inhibition of calcium channel currents in four types of rat sensory neurons differentiated by membrane properties., J Neurophysiol, 74, 1870, 10.1152\u002Fjn.1995.74.5.1870",{"doi":1082},"10.1152\u002Fjn.1995.74.5.1870",{"id":24,"text":1084,"url":24,"identifiers":1085},"10.1038\u002F39807",{"doi":1084},{"id":24,"text":1087,"url":24,"identifiers":1088},"10.1073\u002Fpnas.93.26.15435",{"doi":1087},{"id":24,"text":1090,"url":24,"identifiers":1091},"10.1007\u002FBF01098389",{"doi":1090},{"id":24,"text":1093,"url":24,"identifiers":1094},"10.1073\u002Fpnas.95.15.8963",{"doi":1093},{"id":24,"text":1096,"url":24,"identifiers":1097},"10.1111\u002Fj.1469-7793.1998.857ba.x",{"doi":1096},{"id":24,"text":1099,"url":24,"identifiers":1100},"10.1016\u002F0006-8993(80)90844-6",{"doi":1099},{"id":24,"text":1102,"url":24,"identifiers":1103},"10.1016\u002F0306-4522(95)00433-5",{"doi":1102},{"id":24,"text":1105,"url":24,"identifiers":1106},"Koerber, 1988, Properties of somata of spinal dorsal root ganglion cells differ according to peripheral receptor innervated., J Neurophysiol, 60, 1584, 10.1152\u002Fjn.1988.60.5.1584",{"doi":1107},"10.1152\u002Fjn.1988.60.5.1584",{"id":24,"text":1109,"url":24,"identifiers":1110},"Koltzenburg, 1997, Receptive properties of mouse sensory neurons innervating hairy skin., J Neurophysiol, 78, 1841, 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1988, Dynamic regulation of calcium influx by G-proteins, action potential waveform, and neuronal firing frequency., J Neurosci, 18, 6757, 10.1523\u002FJNEUROSCI.18-17-06757.1998",{"doi":1154},"10.1523\u002FJNEUROSCI.18-17-06757.1998",{"id":24,"text":1156,"url":24,"identifiers":1157},"10.1523\u002FJNEUROSCI.12-06-02104.1992",{"doi":1156},{"id":24,"text":1159,"url":24,"identifiers":1160},"Rueff, 1996, Nerve growth factor and NT-5 induce increased thermal sensitivity of cutaneous nociceptors in vitro., J Neurophysiol, 76, 3593, 10.1152\u002Fjn.1996.76.5.3593",{"doi":1161},"10.1152\u002Fjn.1996.76.5.3593",{"id":24,"text":1163,"url":24,"identifiers":1164},"10.1074\u002Fjbc.271.11.5953",{"doi":1163},{"id":24,"text":1166,"url":24,"identifiers":1167},"Sigworth FJ (1995) Electronic design of the patch clamp. in Single channel recording, eds Sakmann B Neher E (Plenum Press, New York), pp 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brain sodium channel (BNaC, also known as BNC\u002FASIC) proteins form acid-sensitive and amiloride-blockable sodium channels that are related to putative mechanosensory channels. Certain BNaC isoforms are expressed exclusively in dorsal root ganglia (DRG) and have been proposed to form the ion channels mediating tissue acidosis-induced pain. With antibody labeling, we find that the BNaC1α isoform is expressed by most large DRG neurons (low-threshold mechanosensors not involved in acid-induced nociception) and few small nociceptor neurons (which include high-threshold mechanoreceptors). BNaC1α is transported from DRG cell bodies to sensory terminals in the periphery, but not to the spinal cord, and is located specifically at specialized cutaneous mechanosensory terminals, including Meissner, Merkel, penicillate, reticular, lanceolate, and hair follicle palisades as well as some intraepidermal and free myelinated nerve endings. Accordingly, BNaC1α channels might participate in the transduction of touch and painful mechanical stimuli.\u003C\u002Fjats:p>",{"EN":1210},"Transport and Localization of the DEG\u002FENaC Ion Channel BNaC1α to Peripheral Mechanosensory Terminals of Dorsal Root Ganglia Neurons",{"VOID":1212},"11306621",{"VOID":1214},"10.1523\u002Fjneurosci.21-08-02678.2001","2024-09-04T23:57:26.990+00:00",[126],"https:\u002F\u002Fwww.jneurosci.org\u002Flookup\u002Fdoi\u002F10.1523\u002FJNEUROSCI.21-08-02678.2001",[1219,1240,1260,1277,1292],{"id":1220,"sortIndex":25,"researcher":24,"roles":1221,"affiliations":1222,"properties":1233},"68fa034d-773d-4bbc-a423-36065baf0bdb",[],[1223],{"id":1224,"sortIndex":25,"affiliation":1225,"properties":24},"9a3a650e-15d2-418b-b569-1c04ca96a696",{"id":1226,"createTime":1227,"updateTime":1227,"relativeEntities":1228,"slug":1229,"properties":1230,"entityType":45,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"4188ea79-c100-4438-9851-086f32b55954","2024-09-04T23:57:27.013+00:00",[],"Howard-Hughes-Medical-Institute-and-Department-of-Neurobiology-Massachusetts-General-Hospital-and-Harvard-Medical-School-Boston-Massachusetts-02114-and",{"title":1231},{"EN":1232},"Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, and",{"openalex":1234,"orcid":1236,"title":1238},{"VOID":1235},"A5027048040",{"VOID":1237},"https:\u002F\u002Forcid.org\u002F0000-0001-6561-9048",{"EN":1239},"Jaime Garcı́a-Añoveros",{"id":1241,"sortIndex":200,"researcher":24,"roles":1242,"affiliations":1243,"properties":1255},"c657e92c-55f1-4315-84ec-9bdc6578c952",[],[1244],{"id":1245,"sortIndex":25,"affiliation":1246,"properties":24},"61b2821a-d858-4b55-906b-eba86d49fd15",{"id":1247,"createTime":1248,"updateTime":1249,"relativeEntities":1250,"slug":1251,"properties":1252,"entityType":45,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"ef854f67-ee5e-499b-8297-cdd91c8dd609","2023-12-07T08:13:05.987+00:00","2024-09-04T23:57:27.043+00:00",[],"Neural-Plasticity-Research-Group-Department-of-Anesthesia-and-Critical-Care-Massachusetts-General-Hospital-and-Harvard-Medical-School-Charlestown-Massachusetts-02129",{"title":1253},{"VI":1254},"Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129",{"openalex":1256,"title":1258},{"VOID":1257},"A5073472873",{"EN":1259},"Tarek A. 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1973, The free penicillate nerve endings of the human hairy skin., J Anat, 115, 277",{},{"id":24,"text":1393,"url":24,"identifiers":1394},"10.1083\u002Fjcb.8.2.467",{"doi":1393},{"id":24,"text":1396,"url":24,"identifiers":1397},"10.1073\u002Fpnas.95.17.10240",{"doi":1396},{"id":24,"text":1399,"url":24,"identifiers":1400},"10.1126\u002Fscience.273.5273.323",{"doi":1399},{"id":24,"text":1402,"url":24,"identifiers":1403},"10.1006\u002Fbbrc.1998.8183",{"doi":1402},{"id":24,"text":1405,"url":24,"identifiers":1406},"10.1038\u002F349588a0",{"doi":1405},{"id":24,"text":1408,"url":24,"identifiers":1409},"10.1016\u002FS0896-6273(00)80661-3",{"doi":1408},{"id":24,"text":1411,"url":24,"identifiers":1412},"10.1016\u002FS0960-9822(00)00478-4",{"doi":1411},{"id":24,"text":1414,"url":24,"identifiers":1415},"Fricke, 2000, Epithelial Na+ channels and stomatin are expressed in rat trigeminal mechanosensory neurons., Cell Tissue Res, 299, 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1995, RT97: a marker for capsaicin-insensitive sensory endings in the rat skin., Cell Tissue Res, 282, 155, 10.1007\u002FBF00319142",{"doi":1482},"10.1007\u002FBF00319142",{"id":24,"text":1484,"url":24,"identifiers":1485},"Sinclair DC (1982) Mechanisms of cutaneous sensation. (Oxford UP, London).",{},{"id":24,"text":1487,"url":24,"identifiers":1488},"10.1523\u002FJNEUROSCI.12-01-00086.1992",{"doi":1487},{"id":24,"text":1490,"url":24,"identifiers":1491},"10.1146\u002Fannurev.physiol.59.1.633",{"doi":1490},{"id":24,"text":1493,"url":24,"identifiers":1494},"10.1016\u002FS0896-6273(01)80050-7",{"doi":1493},{"id":24,"text":1496,"url":24,"identifiers":1497},"10.1016\u002F0006-8993(83)90241-X",{"doi":1496},{"id":24,"text":1179,"url":24,"identifiers":1499},{"doi":1179},{"id":24,"text":1189,"url":24,"identifiers":1501},{"doi":1189},{"id":24,"text":1503,"url":24,"identifiers":1504},"10.1016\u002FS0959-4388(98)80070-6",{"doi":1503},{"id":24,"text":1506,"url":24,"identifiers":1507},"10.1074\u002Fjbc.271.18.10433",{"doi":1506},{"id":24,"text":1509,"url":24,"identifiers":1510},"10.1074\u002Fjbc.272.34.20975",{"doi":1509},{"id":1512,"createTime":1513,"updateTime":1513,"relativeEntities":1514,"slug":1515,"properties":1516,"entityType":122,"verifyStatus":123,"verifyTime":1513,"verifyNote":124,"syncStatus":23,"languages":1532,"translateLanguages":24,"viewCount":25,"primaryUrl":1533,"fullTextUrl":24,"authors":1534,"publicationType":417,"publisherRelationship":1572,"citationCount":1604,"citationInfo":1605,"publishDate":1608,"publishYear":1609,"citationAnalyzeStatus":23,"lastCitationAnalyze":24,"indexDatabases":24,"openAccess":24,"references":1610,"isForceReanalyzing":622},"eb78524f-6f7e-4bc8-af04-4b024393793a","2024-07-18T23:56:13.789+00:00",[],"Coincident-Activation-of-NMDA-and-Dopamine-D-sub-1-sub-Receptors-within-the-Nucleus-Accumbens-Core-Is-Required-for-Appetitive-Instrumental-Learning",{"mag":1517,"keywords":1519,"pmc":1520,"openalex":1522,"abstract":1524,"title":1526,"pm":1528,"doi":1530},{"VOID":1518},"2096178360",{},{"VOID":1521},"6772875",{"VOID":1523},"W2096178360",{"EN":1525},"\u003Cjats:p>The nucleus accumbens, a brain structure ideally situated to act as an interface between corticolimbic information-processing regions and motor output systems, is well known to subserve behaviors governed by natural reinforcers. In the accumbens core, glutamatergic input from its corticolimbic afferents and dopaminergic input from the ventral tegmental area converge onto common dendrites of the medium spiny neurons that populate the accumbens. We have previously found that blockade of NMDA receptors in the core with the antagonist 2-amino-5-phosphonopentanoic acid (AP-5; 5 nmol) abolishes acquisition but not performance of an appetitive instrumental learning task (Kelley et al., 1997). Because it is currently hypothesized that concurrent dopamine D\u003Cjats:sub>1\u003C\u002Fjats:sub>and glutamate receptor activation is required for long-term changes associated with plasticity, we wished to examine whether the dopamine system in the accumbens core modulates learning via NMDA receptors. Co-infusion of low doses of the D\u003Cjats:sub>1\u003C\u002Fjats:sub>receptor antagonist SCH-23390 (0.3 nmol) and AP-5 (0.5 nmol) into the accumbens core strongly impaired acquisition of instrumental learning (lever pressing for food), whereas when infused separately, these low doses had no effect. Infusion of the combined low doses had no effect on indices of feeding and motor activity, suggesting a specific effect on learning. We hypothesize that co-activation of NMDA and D\u003Cjats:sub>1\u003C\u002Fjats:sub>receptors in the nucleus accumbens core is a key process for acquisition of appetitive instrumental learning. Such an interaction is likely to promote intracellular events and gene regulation necessary for synaptic plasticity and is supported by a number of cellular models.\u003C\u002Fjats:p>",{"EN":1527},"Coincident Activation of NMDA and Dopamine D\u003Csub>1\u003C\u002Fsub>Receptors within the Nucleus Accumbens Core Is Required for Appetitive Instrumental Learning",{"VOID":1529},"11027236",{"VOID":1531},"10.1523\u002Fjneurosci.20-20-07737.2000",[126],"https:\u002F\u002Fwww.jneurosci.org\u002Flookup\u002Fdoi\u002F10.1523\u002FJNEUROSCI.20-20-07737.2000",[1535,1557],{"id":1536,"sortIndex":25,"researcher":24,"roles":1537,"affiliations":1538,"properties":1550},"822db946-77fb-479c-af7c-b78e9856c9fe",[],[1539],{"id":1540,"sortIndex":25,"affiliation":1541,"properties":24},"af5ed67f-d8a8-459a-8896-c17e467fb0d2",{"id":1542,"createTime":1543,"updateTime":1544,"relativeEntities":1545,"slug":1546,"properties":1547,"entityType":45,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"98fb1a0c-5770-4e73-837a-28e6cde46c93","2024-07-18T23:56:13.883+00:00","2024-12-05T12:25:09.052+00:00",[],"Department-of-Psychiatry-University-of-Wisconsin-Madison-Madison-Wisconsin-53719",{"title":1548},{"EN":1549},"Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin 53719",{"openalex":1551,"orcid":1553,"title":1555},{"VOID":1552},"A5052364943",{"VOID":1554},"https:\u002F\u002Forcid.org\u002F0000-0001-7208-159X",{"EN":1556},"Stephanie L. Smith‐Roe",{"id":1558,"sortIndex":200,"researcher":24,"roles":1559,"affiliations":1560,"properties":1567},"e409e7de-2b36-4758-b82a-2f167422a849",[],[1561],{"id":1562,"sortIndex":25,"affiliation":1563,"properties":24},"30416af9-7f49-46a4-82ee-b99d16ba8e45",{"id":1542,"createTime":1543,"updateTime":1544,"relativeEntities":1564,"slug":1546,"properties":1565,"entityType":45,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},[],{"title":1566},{"EN":1549},{"openalex":1568,"title":1570},{"VOID":1569},"A5018633729",{"EN":1571},"Ann E. Kelley",{"url":24,"publisher":1573,"properties":1598},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1574,"slug":10,"properties":1575,"entityType":22,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25,"subjectFields":1581,"manageAffiliations":1582,"indexDatabases":1583,"url":96,"thumbnailPath":24,"statistic":24,"gsStatistic":24,"type":24,"analyzePriority":24},[],{"country":1576,"issn":1577,"introduce":1578,"eissn":1579,"title":1580},{"VOID":13},{"VOID":15},{"EN":17},{"VOID":19},{"EN":21},[],[],[1584,1591],{"id":59,"indexDatabase":1585,"url":74,"indexYears":24,"academicFieldIds":1590,"indexDatabaseRanking":24},{"id":61,"createTime":62,"updateTime":63,"relativeEntities":1586,"label":1587,"description":1588,"key":70,"publicationTags":1589,"standard":24},[],{"EN":66,"VI":66},{"VI":68,"EN":69},[72,73],[76],{"id":78,"indexDatabase":1592,"url":91,"indexYears":92,"academicFieldIds":1597,"indexDatabaseRanking":95},{"id":80,"createTime":81,"updateTime":82,"relativeEntities":1593,"label":1594,"description":1595,"key":88,"publicationTags":1596,"standard":24},[],{"EN":85,"VI":85},{"EN":85,"VI":87},[90],[94],{"volume":1599,"pages":1601,"issue":1603},{"VOID":1600},"20",{"VOID":1602},"7737-7742",{"VOID":1600},318,{"total":1604,"publishYear":24,"statisticByYear":1606},{"2012":1607,"2013":459,"2014":1607,"2015":455,"2016":1346,"2017":1346,"2018":219,"2019":219,"2020":1345,"2021":458,"2022":459,"2023":1345},18,"2000-10-15",2000,[1611,1614,1617,1621,1624,1627,1630,1633,1636,1639,1642,1645,1648,1651,1654,1657,1660,1663,1666,1669,1672,1675,1679,1682,1686,1689,1693,1696,1699,1702,1705,1708,1711,1714,1718,1721,1724,1727,1730,1734,1737,1740,1743,1746,1749,1752,1756,1759],{"id":24,"text":1612,"url":24,"identifiers":1613},"10.1007\u002Fs002210050544",{"doi":1612},{"id":24,"text":1615,"url":24,"identifiers":1616},"Baldwin, 1999, cAMP-dependent protein kinase within the nucleus accumbens core mediate appetitive instrumental learning., Soc Neurosci Abstr, 25, 638",{},{"id":24,"text":1618,"url":24,"identifiers":1619},"Baldwin, 2000, N-Methyl-d-aspartate receptor-dependent plasticity within a distributed corticostriatal network mediates appetitive instrumental learning., Behav Neurosci, 114, 1, 10.1037\u002F0735-7044.114.1.84",{"doi":1620},"10.1037\u002F0735-7044.114.1.84",{"id":24,"text":1622,"url":24,"identifiers":1623},"10.1016\u002F0165-0173(83)90038-3",{"doi":1622},{"id":24,"text":1625,"url":24,"identifiers":1626},"10.1016\u002FS0165-0173(98)00019-8",{"doi":1625},{"id":24,"text":1628,"url":24,"identifiers":1629},"10.1016\u002F0306-4522(93)90488-2",{"doi":1628},{"id":24,"text":1631,"url":24,"identifiers":1632},"10.1016\u002F0306-4522(87)90239-9",{"doi":1631},{"id":24,"text":1634,"url":24,"identifiers":1635},"10.1016\u002F0166-2236(96)81862-5",{"doi":1634},{"id":24,"text":1637,"url":24,"identifiers":1638},"10.1159\u002F000017294",{"doi":1637},{"id":24,"text":1640,"url":24,"identifiers":1641},"10.1073\u002Fpnas.90.20.9576",{"doi":1640},{"id":24,"text":1643,"url":24,"identifiers":1644},"10.1152\u002Fjn.1998.79.1.82",{"doi":1643},{"id":24,"text":1646,"url":24,"identifiers":1647},"10.1073\u002Fpnas.94.13.7036",{"doi":1646},{"id":24,"text":1649,"url":24,"identifiers":1650},"10.1007\u002FBF02247489",{"doi":1649},{"id":24,"text":1652,"url":24,"identifiers":1653},"10.1002\u002F(SICI)1098-2396(199703)25:3\u003C227::AID-SYN1>3.0.CO;2-D",{"doi":1652},{"id":24,"text":1655,"url":24,"identifiers":1656},"10.1016\u002F0306-4522(90)90221-O",{"doi":1655},{"id":24,"text":1658,"url":24,"identifiers":1659},"10.1016\u002FS0149-7634(89)80018-1",{"doi":1658},{"id":24,"text":1661,"url":24,"identifiers":1662},"10.1007\u002FBF00428696",{"doi":1661},{"id":24,"text":1664,"url":24,"identifiers":1665},"10.1002\u002Fcne.902580302",{"doi":1664},{"id":24,"text":1667,"url":24,"identifiers":1668},"10.1097\u002F00001756-199707070-00019",{"doi":1667},{"id":24,"text":1670,"url":24,"identifiers":1671},"10.1523\u002FJNEUROSCI.17-14-05271.1997",{"doi":1670},{"id":24,"text":1673,"url":24,"identifiers":1674},"10.1523\u002FJNEUROSCI.17-09-03334.1997",{"doi":1673},{"id":24,"text":1676,"url":24,"identifiers":1677},"Houk JC Adams JL Barto AG (1995) A model of how the basal ganglia generate and use neural signals that predict reinforcement. in Models of information processing in the basal ganglia, eds Houk JC Davis JL Beiser DG (MIT, Cambridge, MA), pp 249–270.",{"doi":1678},"10.7551\u002Fmitpress\u002F4708.001.0001",{"id":24,"text":1680,"url":24,"identifiers":1681},"10.1016\u002FS0304-3940(97)13443-7",{"doi":1680},{"id":24,"text":1683,"url":24,"identifiers":1684},"Kelley, 1999, Neural integrative activities of nucleus accumbens subregions in relation to motivation and learning., Psychobiology, 27, 198, 10.3758\u002FBF03332114",{"doi":1685},"10.3758\u002FBF03332114",{"id":24,"text":1687,"url":24,"identifiers":1688},"10.1073\u002Fpnas.94.22.12174",{"doi":1687},{"id":24,"text":1690,"url":24,"identifiers":1691},"Kiyatkin, 1996, Dopaminergic modulation of glutamate-induced excitations of neurons in the neostriatum and nucleus accumbens of awake, unrestrained rats., J Neurophysiol, 75, 142, 10.1152\u002Fjn.1996.75.1.142",{"doi":1692},"10.1152\u002Fjn.1996.75.1.142",{"id":24,"text":1694,"url":24,"identifiers":1695},"10.1038\u002F368242a0",{"doi":1694},{"id":24,"text":1697,"url":24,"identifiers":1698},"10.1523\u002FJNEUROSCI.16-13-04231.1996",{"doi":1697},{"id":24,"text":1700,"url":24,"identifiers":1701},"10.1016\u002F0301-0082(94)90037-X",{"doi":1700},{"id":24,"text":1703,"url":24,"identifiers":1704},"10.1074\u002Fjbc.272.18.12107",{"doi":1703},{"id":24,"text":1706,"url":24,"identifiers":1707},"10.1073\u002Fpnas.96.6.3239",{"doi":1706},{"id":24,"text":1709,"url":24,"identifiers":1710},"10.1523\u002FJNEUROSCI.16-18-05870.1996",{"doi":1709},{"id":24,"text":1712,"url":24,"identifiers":1713},"Lindvall, 1978, Anatomy of the dopaminergic neuron systems in the rat brain., Adv Biochem Psychopharmacol, 19, 1",{},{"id":24,"text":1715,"url":24,"identifiers":1716},"Lovinger, 1993, Short- and long-term synaptic depression in rat neostriatum., J Neurophysiol, 70, 1937, 10.1152\u002Fjn.1993.70.5.1937",{"doi":1717},"10.1152\u002Fjn.1993.70.5.1937",{"id":24,"text":1719,"url":24,"identifiers":1720},"10.1016\u002F0006-8993(77)91003-4",{"doi":1719},{"id":24,"text":1722,"url":24,"identifiers":1723},"10.1111\u002Fj.1460-9568.1993.tb00475.x",{"doi":1722},{"id":24,"text":1725,"url":24,"identifiers":1726},"10.1016\u002F0306-4522(95)00012-8",{"doi":1725},{"id":24,"text":1728,"url":24,"identifiers":1729},"10.1016\u002F0361-9230(88)90136-0",{"doi":1728},{"id":24,"text":1731,"url":24,"identifiers":1732},"Salamone JD (1987) The actions of neuroleptic drugs on appetitive instrumental behaviors. in Handbook of psychopharmacology, Vol 19, eds Iversen LL Iversen SD Snyder SH (Plenum, New York), pp 575–608.",{"doi":1733},"10.1007\u002F978-1-4613-1819-4_10",{"id":24,"text":1735,"url":24,"identifiers":1736},"10.1126\u002Fscience.275.5306.1593",{"doi":1735},{"id":24,"text":1738,"url":24,"identifiers":1739},"10.1016\u002F0006-8993(90)91146-8",{"doi":1738},{"id":24,"text":1741,"url":24,"identifiers":1742},"10.1016\u002F0166-2236(90)90106-K",{"doi":1741},{"id":24,"text":1744,"url":24,"identifiers":1745},"10.1037\u002F0735-7044.113.4.703",{"doi":1744},{"id":24,"text":1747,"url":24,"identifiers":1748},"Totterdell, 1989, Convergence of hippocampal and DA-ergic input onto identified neurons in the nucleus accumbens of the rat., J Chem Neuroanat, 2, 285",{},{"id":24,"text":1750,"url":24,"identifiers":1751},"10.1016\u002F0006-8993(86)90760-2",{"doi":1750},{"id":24,"text":1753,"url":24,"identifiers":1754},"Walaas, 1979, The effects of surgical and chemical lesions on neurotransmitter candidates on the nucleus accumbens., Neuroscience, 4, 209, 10.1016\u002F0306-4522(79)90083-6",{"doi":1755},"10.1016\u002F0306-4522(79)90083-6",{"id":24,"text":1757,"url":24,"identifiers":1758},"10.1016\u002F0306-4522(95)00436-M",{"doi":1757},{"id":24,"text":1760,"url":24,"identifiers":1761},"Young, 1986, Excitatory amino acid neurotransmitters in the corticostriate pathway: studies using intracerebral microdialysis in vivo., J Neurochem, 47, 1399, 10.1111\u002Fj.1471-4159.1986.tb00771.x",{"doi":1762},"10.1111\u002Fj.1471-4159.1986.tb00771.x",{"id":1764,"createTime":1765,"updateTime":1765,"relativeEntities":1766,"slug":1767,"properties":1768,"entityType":122,"verifyStatus":123,"verifyTime":1765,"verifyNote":124,"syncStatus":23,"languages":1784,"translateLanguages":24,"viewCount":25,"primaryUrl":1785,"fullTextUrl":24,"authors":1786,"publicationType":417,"publisherRelationship":2005,"citationCount":2038,"citationInfo":2039,"publishDate":2041,"publishYear":2042,"citationAnalyzeStatus":23,"lastCitationAnalyze":24,"indexDatabases":24,"openAccess":24,"references":2043,"isForceReanalyzing":622},"8faf10a4-d2e9-4c17-b0fb-41ffe20782b9","2024-07-18T23:55:59.599+00:00",[],"Polymorphisms-in-the-Taste-Receptor-Gene-i-Tas1r3-i-Region-Are-Associated-with-Saccharin-Preference-in-30-Mouse-Strains",{"mag":1769,"keywords":1771,"pmc":1772,"openalex":1774,"abstract":1776,"title":1778,"pm":1780,"doi":1782},{"VOID":1770},"2116471790",{},{"VOID":1773},"1397915",{"VOID":1775},"W2116471790",{"EN":1777},"\u003Cjats:p>The results of recent studies suggest that the mouse\u003Cjats:italic>Sac\u003C\u002Fjats:italic>(saccharin preference) locus is identical to the\u003Cjats:italic>Tas1r3\u003C\u002Fjats:italic>(taste receptor) gene. The goal of this study was to identify\u003Cjats:italic>Tas1r3\u003C\u002Fjats:italic>sequence variants associated with saccharin preference in a large number of inbred mouse strains. Initially, we sequenced ∼6.7 kb of the\u003Cjats:italic>Tas1r3\u003C\u002Fjats:italic>gene and its flanking regions from six inbred mouse strains with high and low saccharin preference, including the strains in which the\u003Cjats:italic>Sac\u003C\u002Fjats:italic>alleles were described originally (C57BL\u002F6J,\u003Cjats:italic>Sac\u003Cjats:sup>b\u003C\u002Fjats:sup>\u003C\u002Fjats:italic>; DBA\u002F2J,\u003Cjats:italic>Sac\u003Cjats:sup>d\u003C\u002Fjats:sup>\u003C\u002Fjats:italic>). Of the 89 sequence variants detected among these six strains, eight polymorphic sites were significantly associated with preferences for 1.6 m\u003Cjats:sc>m\u003C\u002Fjats:sc>saccharin. Next, each of these eight variant sites were genotyped in 24 additional mouse strains. Analysis of the genotype–phenotype associations in all 30 strains showed the strongest association with saccharin preference at three sites: nucleotide (nt) –791 (3 bp insertion\u002Fdeletion), nt +135 (Ser45Ser), and nt +179 (Ile60Thr). We measured\u003Cjats:italic>Tas1r3\u003C\u002Fjats:italic>gene expression, transcript size, and T1R3 immunoreactivity in the taste tissue of two inbred mouse strains with different\u003Cjats:italic>Tas1r3\u003C\u002Fjats:italic>haplotypes and saccharin preferences. The results of these experiments suggest that the polymorphisms associated with saccharin preference do not act by blocking gene expression, changing alternative splicing, or interfering with protein translation in taste tissue. The amino acid substitution (Ile60Thr) may influence the ability of the protein to form dimers or bind sweeteners. Here, we present data for future studies directed to experimentally confirm the function of these polymorphisms and highlight some of the difficulties of identifying specific DNA sequence variants that underlie quantitative trait loci.\u003C\u002Fjats:p>",{"EN":1779},"Polymorphisms in the Taste Receptor Gene (\u003Ci>Tas1r3\u003C\u002Fi>) Region Are Associated with Saccharin Preference in 30 Mouse Strains",{"VOID":1781},"14749438",{"VOID":1783},"10.1523\u002Fjneurosci.1374-03.2004",[126],"https:\u002F\u002Fwww.jneurosci.org\u002Flookup\u002Fdoi\u002F10.1523\u002FJNEUROSCI.1374-03.2004",[1787,1807,1839,1856,1875,1890,1907,1924,1941,1962,1988],{"id":1788,"sortIndex":189,"researcher":24,"roles":1789,"affiliations":1790,"properties":1802},"c935a13b-0127-4ccb-b0ad-f86f14669fac",[],[1791],{"id":1792,"sortIndex":25,"affiliation":1793,"properties":24},"ac1b4ef2-acc8-4453-ab7f-c2173c96c74b",{"id":1794,"createTime":1795,"updateTime":1796,"relativeEntities":1797,"slug":1798,"properties":1799,"entityType":45,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"ac493e45-f4a6-4fb5-905e-6190aa208fa5","2024-07-18T23:55:59.627+00:00","2024-12-03T18:34:45.542+00:00",[],"Monell-Chemical-Senses-Center-3500-Market-Street-Philadelphia-PA-19104-",{"title":1800},{"EN":1801},"Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104.",{"openalex":1803,"title":1805},{"VOID":1804},"A5079651074",{"EN":1806},"X. Li",{"id":1808,"sortIndex":1346,"researcher":24,"roles":1809,"affiliations":1810,"properties":1832},"572bda89-824e-4db8-bb8d-2ffbf6b2e13f",[],[1811,1821],{"id":1812,"sortIndex":25,"affiliation":1813,"properties":24},"0e371811-6851-4b4e-9104-46f897fcb5a1",{"id":1814,"createTime":1815,"updateTime":1815,"relativeEntities":1816,"slug":1817,"properties":1818,"entityType":45,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"244f19ab-429e-4f3e-966c-559ce542c8fd","2024-07-18T23:55:59.694+00:00",[],"Department-of-Psychology-and-School-of-Veterinary-Medicine-University-of-Pennsylvania-Philadelphia-Pennsylvania-19104",{"title":1819},{"EN":1820},"Department of Psychology and School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104",{"id":1822,"sortIndex":200,"affiliation":1823,"properties":24},"f734b7a7-6b53-4b01-a4f5-93308d862868",{"id":1824,"createTime":1825,"updateTime":1826,"relativeEntities":1827,"slug":1828,"properties":1829,"entityType":45,"verifyStatus":23,"verifyTime":24,"verifyNote":24,"syncStatus":23,"languages":24,"translateLanguages":24,"viewCount":25},"b005d196-3048-4da1-984e-b90768e7bdc6","2024-01-16T05:23:09.052+00:00","2024-10-16T15:39:12.072+00:00",[],"Monell-Chemical-Senses-Center-Philadelphia-Pennsylvania-19104",{"title":1830},{"VI":1831},"Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104",{"openalex":1833,"orcid":1835,"title":1837},{"VOID":1834},"A5102740667",{"VOID":1836},"https:\u002F\u002Forcid.org\u002F0000-0001-9805-0847",{"EN":1838},"Gary K. 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The binding of [3H]N6-cyclohexyladenosine to slide-mounted rat brain tissue sections has the characteristics of A1 receptors. It is saturable with high affinity and has appropriate pharmacology and stereospecificity. The highest densities of adenosine receptors occur in the molecular layer of the cerebellum, the molecular and polymorphic layers of the hippocampus and dentate gyrus, the medial geniculate body, certain thalamic nuclei, and the lateral septum. High densities also are observed in certain layers of the cerebral cortex, the piriform cortex, the caudate-putamen, the nucleus accumbens, and the granule cell layer of the cerebellum. Most white matter areas, as well as certain gray matter areas, such as the hypothalamus, have negligible receptor concentrations. 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Although tumor suppressor genes appear to play a general role in regulating cellular proliferation, the normal biological function of the APC gene product is unknown. In the present study, we cloned fragments of the rat homolog of the APC gene and examined its tissue distribution by Northern blot analysis. These studies demonstrated particularly high levels of APC mRNA in brain. To gain clues to the role of the APC gene in brain function, we examined the neuroanatomical distribution of APC mRNA using in situ hybridization. In the adult, prominent expression of APC mRNA was observed in the olfactory bulb, hippocampus, and cerebellum, with low levels of hybridization in other regions of adult rat brain. In contrast, during embryonic and early postnatal development (1–2 weeks), high levels of APC expression were found throughout the brain and then decreased to adult levels by 6 weeks after birth, except in the olfactory bulb where the high levels of APC mRNA found in development persist in the adult. During development of cortex, cerebellum, and retina, APC mRNA expression was particularly prominent in layers containing newly formed postmitotic neurons, with lower levels observed in the proliferative zones where neurogenesis occurs. 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