BILATERAL ACTIONS OF THE RETICULOSPINAL TRACT IN THE MONKEY DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of the Ohio State University By Adam G. Davidson * * * * * The Ohio State University 2004 Dissertation Committee Approved by Dr. John A. Buford, Adviser Dr. Georgia A. Bishop ________________________________ Adviser Dr. Jacqueline Bresnahan Neuroscience Graduate Studies Program Copyright by Adam G. Davidson 2004 ii ABSTRACT The motor output of the primate pontomedullary reticular formation (PMRF) was investigated with spike- and stimulus triggered averaging (SpikeTA, StimulusTA) in monkeys during reaching. The first study employed StimulusTA for ipsilateral arm and shoulder muscles and bilateral trapezius muscles. The second study used StimulusTA and SpikeTA for 24 muscles. Muscles studied on the ipsilateral (i) and contralateral (c) side were extensor carpi ulnaris (ECU), flexor carpi radialis (FCR), brachioradialis (Brac), biceps (Bic), triceps-long head (TrLo), triceps-lateral head (TrLa), anterior deltoid (ADlt), posterior deltoid (PDlt), latissimus dorsi (Lat), pectoralis major (PMj), middle trapezius (MTr), and upper trapezius (UTr). Average onset was significantly earlier for post-stimulus facilitation (PStF) than for post-stimulus suppression (PStS). The average duration of PStS was longer than the average duration of PStF, and response magnitude was significantly larger for PStF. A clear pattern of PStF and PStS was observed among all muscles. In the ipsilateral arm, flexors were facilitated and extensors were suppressed. In the contralateral arm, extensors were facilitated and flexors were suppressed. Shoulder girdle muscles demonstrated similar proportions for responses: iUTr, cMTr, and cPMj were suppressed; cUTr , iMTr, and iPMj were facilitated. Lat was the only muscle to demonstrate the same response (PStS) bilaterally. Reciprocal, cofacilitation, and cosuppression responses were observed between anatomical antagonists within a limb iii and bilateral homologues at individual stimulus sites. These responses were usually reciprocal and matched the most prevalent response for each member of the pair. Overall, 9 of 368 cells produced post-spike effects (PSpEs). 8 of the 11 total PSpEs were post spike facilitation (PSpF). 4 PSpEs matched the corresponding PStE obtained at the same site. Overall, StimulusTA and SpikeTA of bilateral arm and shoulder muscles revealed motor patterns that implicate the reticulospinal tract in the control of voluntary reaching movements and the coordination of bilateral movements. iv Dedicated to my wife, Kristen v ACKNOWLEDGMENTS First, I wish to thank my advisor, John Buford, PhD, for his guidance and support throughout this dissertation and during the past four years of graduate school. I also wish to thank Stephanie Moran for all of her technical assistance in the lab. Thanks to Dr. S. T. Sakai for assistance with the anatomical investigations performed for these studies. I would like to thank my committee members, Georgia Bishop, PhD and Jacqueline Bresnahan, PhD, for helping me with this dissertation and other endeavors during my graduate career. I would also like to thank other Neuroscience faculty who have helped me along the way, especially Dr. M. Scott Herness for his encouragement and guidance. Thank you to Mom and Dad for your support through the years. To my brother Brian, thanks for setting the example for me. Finally, to Kristen, thank you for your love and support. I could not have done it without you. The experiments presented in this dissertation were supported by NIH grant R01 NS37822. Chapter 2 is included in this dissertation with permission from the American Physiological Society (cited in reference list). Portions of figure 3.12 appear with permission from John Wiley & Sons Inc. All other portions of this dissertation are copyrighted. vi VITA August 7, 1977...…………………….Born – Statesville, North Carolina 2000 – 2001………………………….Interdisciplinary Graduate Program Fellow, The Ohio State University 2001 – present……………………….Graduate Research Assistant, The Ohio State University PUBLICATIONS Davidson, A. G., & Buford, J. A. (2004). Motor output to arm and shoulder muscles from the PMRF of the monkey as revealed by stimulus triggered averaging. Journal of Neurophysiology. 10.1152/jn.00083.2003. Buford, J. A. & Davidson, A. G. (2004). Movement related and preparatory activity in the reticulospinal system of the monkey. Experimental Brain Research. 10.1007/s00221-004-1956-4. FIELD OF STUDY Major Field: Neuroscience vii TABLE OF CONTENTS Page Abstract……………………………………………………………………...……………iii Dedication…..……………………………………………………………………………..v Acknowledgments...……………………………………………………………………...vi Vita………………………………………………………………………………….…...vii List of Tables……………………………………………………………………………...x List of Figures …………………………………………………………………………....xi Chapters: 1. Introduction…..……………………………………………………………………1 1.1 Anatomy of the reticulospinal tracts……………………….………………….2 1.2 Studies of reticulospinal tract function……………………………………......3 Reticulospinal functions in the primate…………………………………...7 1.3 Patterns and organization of reticulospinal motor outputs……………………9 1.4 Mechanisms of reticulospinal actions in the spinal cord………………….…11 1.5 Spike and stimulus triggered averaging………..…………………………….16 2. Motor outputs from the primate reticular formation to arm and shoulder muscles as revealed by stimulus-triggered averaging ……....………...………………….20 2.1. Abstract….………………...…………………………….…………………..20 2.2. Introduction….…………………….…………………….…………………..21 2.3. Methods…….……………………….……………….....……………………24 viii 2.4. Results………………………………………………………………….........31 2.5. Discussion…………………….……………………………………………..39 3. Bilateral actions of the reticulospinal tract on arm and shoulder muscles in the monkey: Spike and stimulus triggered averaging ...………...………………….62 3.1. Abstract….………..…………………………….…………………..62 3.1. Introduction….………………………………….…………………..63 3.2. Methods…….……………………………….....……………………67 3.3. Results…………………………………………………………........75 3.4. Discussion…………………………………………………………...91 4. Conclusion……………….…………………...………………………………...125 List of References……………………………………………..……………………….128 ix LIST OF TABLES Table Page 2.1 Onset latency and duration of post-stimulus events..……………………………51 3.1 Location of EMG implants …..……………………………..………………….106 3.2 Average onset of PStEs…. …..……………………………..…………….…….107 3.3 Average duration of PStEs…. …..…………………………..………………….108 3.4 Average MPC of PStEs…. …..……………………………..……………….….109 3.5 Average SDPk of PStEs…. …..………...…………………..…………….…….110 x LIST OF FIGURES Figure Page 2.1 Representative sample of EMG during task performance……………………….52 2.2 Anatomical location of effective stimulus sites for ipsilateral upper trapezius………………………………………………………………………….53 2.3 Detection of post-stimulus effects...……………….…………………………….54 2.4 Histograms of onset latency and mean percent change………………………….55 2.5 Histograms of post-stimulus effects by onset latency for each muscle………….56 2.6 Proportions of post-stimulus facilitation and post-stimulus suppression events by muscle……............................................................................................57 2.7 A typical stimulus-triggered average…………………………………………….58 2.8 Additional examples of stimulus-triggered averages…………………………….59 2.9 Large amplitude, short latency response in ipsilateral upper trapezius………….60 2.10 Bilateral responses in upper trapezius……………………………………………61 3.1 Diagram of the behavioral task…………………………………………………112 3.2 Spike and stimulus triggered averaging……………………………………...…113 3.3 Representative sample of EMG during task performance…………………...…114 3.4 Histogram of onset latencies…………………………….…………………...…115 3.5 Effectiveness of stimulation/ Proportion of post-stimulus facilitation……………………………………………….…………………...…116 3.6 Representative stimulus-triggered average……..……….…………………...…117 xi 3.7 Upper trapezius post-stimulus facilitation…...………….…………………...…118 3.8 Concurrent reciprocal response………………………….…………………...…119 3.9 Serial reciprocal response………………………………………………………120 3.10 Representation of frequent responses…………………..………………………121 3.11 Comparison of similar post stimulus and post spike effects..………………..…122 3.12 Anatomical reconstruction of effective stimulus sites………………………….124 xii CHAPTER 1 INTRODUCTION A variety of functions have been attributed to the reticular formation including, but not limited to, REM sleep (Siegel et al., 1981;Siegel et al., 1979), arousal (Steriade, 1996;Steriade et al., 1986;Steriade, 1970;Steriade, 1995;Steriade et al., 1988), sensory modulation (Abols and Basbaum, 1981;Basbaum et al., 1986;Peterson et al., 1974), and the control of gaze (Berthoz and Grantyn, 1986;Grantyn et al., 2004;Grantyn et al., 1993;Grantyn et al., 1987;Grantyn and Berthoz, 1987;Olivier et al., 1993). In addition to these functions, the reticular formation has been implicated in the control of axial and limb muscles for posture and locomotion (Drew and Rossignol, 1984;Drew and Rossignol, 1985;Drew et al., 1986;Drew and Rossignol, 1987;Drew et al., 2004;Schepens and Drew, 2003b), as well as voluntary reaching movements (Buford and Anderson, 1996;Ruffo and Buford, 1997). The exact role the reticulospinal system plays in motor control is not known. In fact, of the four major descending motor systems (the corticospinal, rubrospinal, vestibulospinal, and reticulospinal tract (RST)), the least is known about the reticulospinal system. The majority of what is known about the RST has 1 come from experiments