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Neurodegeneration, which begins in the striatum and then spreads to other brain areas, is preceded by dysfunction in multiple aspects of neurotransmission across a variety of brain areas. This review will provide an overview of the neurochemical mediators and modulators of synaptic transmission that are disrupted in HD. This includes classical neurotransmitters like glutamate and gamma\u2010aminobutyric acid, modulators such as dopamine, adenosine and endocannabinoids, and molecules like brain\u2010derived neurotrophic factor which affect neurotransmission in a more indirect manner. Alterations in the functioning of these signaling pathways can occur across multiple brain regions such as striatum, cortex and hippocampus, and affect transmission and plasticity at the synapses within these regions, which may ultimately change behaviour and contribute to the pathophysiology of HD. The current state of knowledge in this area has already yielded useful information about the causes of synaptic dysfunction and selective cell death. A full understanding of the mechanisms and consequences of disruptions in synaptic function and plasticity will lend insight into the development of the symptoms of HD, and potential drug targets for ameliorating them.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14723-fig-0002-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jnc.14723","type":"journal-article","created":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T14:27:38Z","timestamp":1558016858000},"page":"346-365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":138,"title":["Alterations in synaptic function and plasticity in Huntington disease"],"prefix":"10.1111","volume":"150","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4763-2825","authenticated-orcid":false,"given":"Amy I.","family":"Smith\u2010Dijak","sequence":"first","affiliation":[{"name":"Graduate Program in Neuroscience the University of British Columbia Vancouver British Columbia Canada"},{"name":"Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health the University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja D.","family":"Sepers","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health the University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8610-1042","authenticated-orcid":false,"given":"Lynn A.","family":"Raymond","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health the University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2916-06.2007"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3539-10.2011"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.06.017"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.7b00508"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.08.042"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02839.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.01.006"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004744108"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2015-312413"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf180"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1781(01)00257-8"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq278"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2015.11"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/caff.2018.0006"},{"key":"e_1_2_11_16_1","first-page":"1202","article-title":"The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size","volume":"60","author":"Brinkman R. 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