{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:14:04Z","timestamp":1790327644250,"version":"4.1.0"},"reference-count":230,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005191","name":"Craig H. Neilsen Foundation","doi-asserted-by":"publisher","award":["647662"],"award-info":[{"award-number":["647662"]}],"id":[{"id":"10.13039\/100005191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>During mild or moderate exercise, alveolar ventilation increases in direct proportion to metabolic rate, regulating arterial CO<jats:sub>2<\/jats:sub> pressure near resting levels. Mechanisms giving rise to the hyperpnoea of exercise are unsettled despite over a century of investigation. In the past three decades, neuroscience has advanced tremendously, raising optimism that the \u2018exercise hyperpnoea dilemma\u2019 can finally be solved. In this review, new perspectives are offered in the hope of stimulating original ideas based on modern neuroscience methods and current understanding. We first describe the ventilatory control system and the challenge exercise places upon blood\u2010gas regulation. We highlight relevant system properties, including feedforward, feedback and adaptive (i.e., plasticity) control of breathing. We then elaborate a seldom explored hypothesis that the exercise ventilatory response continuously adapts (learns and relearns) throughout life and ponder if the memory \u2018engram\u2019 encoding the feedforward exercise ventilatory stimulus could reside within the cerebellum. Our hypotheses are based on accumulating evidence supporting the cerebellum's role in motor learning and the numerous direct and indirect projections from deep cerebellar nuclei to brainstem respiratory neurons. We propose that cerebellar learning may be obligatory for the accurate and adjustable exercise hyperpnoea capable of tracking changes in life conditions\/experiences, and that learning arises from specific cerebellar microcircuits that can be interrogated using powerful techniques such as optogenetics and chemogenetics. Although this review is speculative, we consider it essential to reframe our perspective if we are to solve the till\u2010now intractable exercise hyperpnoea dilemma.<\/jats:p>","DOI":"10.1113\/ep091506","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T17:40:48Z","timestamp":1711734048000},"page":"1217-1237","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inaugural Review Prize 2023: The exercise hyperpnoea dilemma: A 21st\u2010century perspective"],"prefix":"10.1113","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9285-7113","authenticated-orcid":false,"given":"Joseph F.","family":"Welch","sequence":"first","affiliation":[{"name":"School of Sport, Exercise and Rehabilitation Sciences, College of Life and Environmental Sciences University of Birmingham  Edgbaston Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon S.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Breathing Research and Therapeutics Centre, Department of Physical Therapy, McKnight Brain Institute University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1984.sp015408"},{"key":"e_1_2_8_3_1","first-page":"P25","article-title":"Associative conditioning of the exercise ventilatory response","volume":"2","author":"Al\u2010Harbi W.","year":"2001","journal-title":"Respiration Physiology"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1937.sp003485"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0025-5564(71)90051-4"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00462.2010"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.213769"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19981130)401:4<455::AID-CNE3>3.0.CO;2-6"},{"issue":"4","key":"e_1_2_8_9_1","first-page":"451","article-title":"Cerebellar projections to limbic system","volume":"22","author":"Anand B. 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