Abstract
Many models of eyeblink conditioning assume that there is a simple linear relationship between the firing patterns of neurons in the interpositus nucleus and the time course of the conditioned response (CR). However, the complexities of muscle behaviour and plant dynamics call this assumption into question. We investigated the issue by implementing the most detailed model available of the rabbit nictitating membrane response (Bartha and Thompson in Biol Cybern 68:135–143, 1992a and in Biol Cybern 68:145–154, 1992b), in which each motor unit of the retractor bulbi muscle is represented by a Hill-type model, driven by a non-linear activation mechanism designed to reproduce the isometric force measurements of Lennerstrand (J Physiol 236:43–55, 1974). Globe retraction and NM extension are modelled as linked second order systems. We derived versions of the model that used a consistent set of SI units, were based on a physically realisable version of calcium kinetics, and used simulated muscle cross-bridges to produce force. All versions showed similar non-linear responses to two basic control strategies. (1) Rate-coding with no recruitment gave a sigmoidal relation between control signal and amplitude of CR, reflecting the measured relation between isometric muscle force and stimulation frequency. (2) Recruitment of similar strength motor units with no rate coding gave a sublinear relation between control signal and amplitude of CR, reflecting the increase in muscle stiffness produced by recruitment. However, the system response could be linearised by either a suitable combination of rate-coding and recruitment, or by simple recruitment of motor units in order of (exponentially) increasing strength. These plausible control strategies, either alone or in combination, would in effect present the cerebellum with the simplified virtual plant that is assumed in many models of eyeblink conditioning. Future work is therefore needed to determine the extent to which motor neuron firing is in fact linearly related to the nictitating membrane response.
Similar content being viewed by others
Abbreviations
- CR:
-
Conditioned response
- HG:
-
Harders gland
- MN:
-
Motoneuron
- MU:
-
Motor unit
- NM:
-
Nictitating membrane
- NMR:
-
Nictitating membrane response
- RB:
-
Retractor bulbi
References
Aksenov D, Serdyukova N, Irwin K, Bracha V (2004) GABA neurotransmission in the cerebellar interposed nuclei: involvement in classically conditioned eyeblinks and neuronal activity. J Neurophysiol 91:719–727
Balkenius C, Morén J (1999) Dynamics of a classical conditioning model. Auton Robots 7:41–56
Bartha GT, Thompson RF (1992a) Control of rabbit nictitating membrane movements: 1. A computer model of the retractor bulbi muscle and the associated orbital mechanics. Biol Cybern 68:135–143
Bartha GT, Thompson RF (1992b) Control of rabbit nictitating membrane movements: II. Analysis of the relation of motoneuron activity to behavior. Biol Cybern 68:145–154
Bers DM (2002) Cardiac excitation–contraction coupling. Nature 415:198–205
Berthier NE, Moore JW (1983) The nictitating membrane response: an electrophysiological study of the abducens nerve and nucleus and the accessory abducens nucleus in rabbit. Brain Res 258:201–210
Berthier NE, Moore JW (1990) Activity of deep cerebellar nuclear cells during classical conditioning of nictitating membrane extension in rabbits. Exp Brain Res 83:44–54
Berthier NE, Barto AG, Moore JW (1991) Linear systems analysis of the relationship between firing of deep cerebellar neurons and the classically conditioned nictitating membrane response in rabbits. Biol Cybern 65:99–106
Bizzi E, Accornero N, Chapple W, Hogan N (1982) Arm trajectory formation in monkeys. Exp Brain Res 46:139–143
Bobet J, Stein RB (1998) A simple model of force generation by skeletal muscle during dynamic isometric movements. IEEE Trans Biomed Eng 45:1010–1016
Bobet J, Gossen ER, Stein RB (2005) A comparison of models of force production during stimulated isometric ankle dorsiflexion in humans. IEEE Trans Neural Syst Rehabil Eng 13:444–451
Brown IE, Loeb GE (2000) Measured and modeled properties of mammalian skeletal muscle: IV. Dynamics of activation and deactivation. J Muscle Res Cell Motil 21:33–47
Cegavske CF, Patterson MM, Thompson RF (1979) Neuronal unit activity in the abducens nucleus during classical conditioning of the nictitating membrane response in the rabbit. J Comp Physiol Psychol 93:595–609
Choi JS, Moore JW (2003) Cerebellar neuronal activity expresses the complex topography of conditioned eyeblink responses. Behav Neurosci 117:1211–1219
Cooper S, Eccles JC (1930) The isometric responses of mammalian muscles. J Physiol 69:375–385
Curtin NA, Gardner-Medwin AR, Woledge RC (1998) Predictions of the time course and power output by dogfish white muscle fibres during brief tetani. J Exp Biol 201:103–114
Dean P (1996) Motor unit recruitment in a distributed model of extraocular muscle. J Neurophysiol 76:727–742
Dean P, Porrill J, Warren PA (1999) Optimality of static force control by horizontal eye muscles: a test of the minimum norm rule. J Neurophysiol 81:735–757
Delgado-García JM, Gruart A (2005) Firing activities of identified posterior interpositus nucleus neurons during associative learning in behaving cats. Brain Res Rev 49:367–376
Ding J, Wexler JS, Binder-MacLeod SA (2002) A mathematical model that predicts the force-frequency relationship of human skeletal muscle. Muscle Nerve 26:477–485
Disterhoft JF, Weiss C (1985) Motoneuronal control of eye retraction/nictitating membrane extension in rabbit. In: Alkon DL, Woody CD (eds) Neural mechanisms of conditioning, Plenum Press, New York, 197–208
Dorgan SJ, O’Malley MJ (1998) A mathematical model for skeletal muscle activated by N-let pulse trains. IEEE Trans Rehabil Eng 6:286–299
Eglitis I (1964) The glands. In: Prince JH (ed) The rabbit in eye research, Charles C Thomas, Springfield, Il, pp 38–56
Evinger C, Manning KA, Sibony PA (1991) Eyelid movements. Mechanisms and normal data. Invest Ophthalmol Visual Sci 32:387–400
Feldman AG (1981) The composition of central programs subserving horizontal eye movements in man. Biol Cybern 42:107–116
Fiala JC, Grossberg S, Bullock D (1996) Metabotropic glutamate receptor activation in cerebellar Purkinje cells as substrate for adaptive timing of the classically conditioned eye-blink response. J Neurosci 16:3760–3774
Freeman JH, Nicholson DA (2000) Developmental changes in eye-blink conditioning and neuronal activity in the cerebellar interpositus nucleus. J Neurosci 20:813–819
Garenne A, Chauvet GA (2004) A discrete approach for a model of temporal learning by the cerebellum: in silico classical conditioning of the eyeblink reflex. J Integr Neurosci 3:301–318
Gluck MA, Allen MT, Myers CE, Thompson RF (2001) Cerebellar substrates for error correction in motor conditioning. Neurobiol Learn Mem 76:314–341
Goldberg SJ (1990) Mechanical properties of extraocular motor units. In: Binder MD, Mendell LM (eds) The segmental motor system. Oxford University Press, New York, pp 222–238
Gruart A, Blázquez P, Delgado-García JM (1995) Kinematics of spontaneous, reflex, and conditioned eyelid movements in the alert cat. J Neurophysiol 74:226–248
Gruart A, Schreurs BG, Del Toro ED, Delgado-García JM (2000) Kinetic and frequency-domain properties of reflex and conditioned eyelid responses in the rabbit. J Neurophysiol 83:836–852
Hannaford B (1990) A nonlinear model of the phasic dynamics of muscle activation. IEEE Trans Biomed Eng 37:1067–1075
Hesslow G, Yeo CH (2002) The functional anatomy of skeletal conditioning. In: Moore JW (ed) A neuroscientist’s guide to classical conditioning. Springer, Berlin Heidelberg New York, pp 86–146
Hofstötter C, Mintz M, Verschure PFMJ (2002) The cerebellum in action: a simulation and robotics study. Eur J Neurosc 16:1361–1376
Hung G, Hsu F, Stark L (1977) Dynamics of the human eye blink. Am J Optom Physiol Opt 54:678–690
Huxley AF (1957) Muscle structure and theories of contraction. Prog Biophys Biophys Chem 7:257–318
Julian FJ (1969) Activation in a skeletal muscle contraction model with modification for insect fibrillar muscle. Biophys J 9:547-570
Kernell D, Eerbeek O, Verhey BA (1983) Relation between isometric force and stimulus rate in cats hindlimb motor units of different twitch contraction time. Exp Brain Res 50:220–227
Leal-Campanario R, Barradas-Bribiescas JA, Delgado-García JM, Gruart A (2004) Relative contributions of eyelid and eye-retraction motor systems to reflex and classically conditioned blink responses in the rabbit. J Appl Physiol 96:1541–1554
Lennerstrand G (1974) Mechanical studies on the retractor bulbi muscle and its motor units in the cat. J Physiol 236:43–55
Lepora NF, Mavritsaki E, Porrill J, Dean P, Yeo CH, Evinger LC (2005) Evidence for linearity in control of nictitating membrane responses by retractor bulbi motor units. In: 2005 Abstract Viewer/Itinerary Planner. Society for Neuroscience, Washington, Prog. No. 869.863
Llinás R, Welsh JP (1993) On the cerebellum and motor learning. Curr Opin Neurobiol 3:958–965
Mauk MD, Medina JF, Nores WL, Ohyama T (2000) Cerebellar function: coordination, learning or timing? Curr Biol 10: R522–R525
Mavritsaki E, Porrill J, Ivarsson M, Yeo CH, Dean P (2001) Recruitment of retractor bulbi motor units in a population model of the nictitating membrane response. Society for Neuroscience Abstracts 27:Prog. no. 405.404
McCormick DA, Thompson RF (1984) Neuronal responses of the rabbit cerebellum during acquisition and performance of a classically conditioned nictitating membrane-eyelid response. J Neurosci 4:2811–2822
Medina JF, Mauk MD (2000) Computer simulation of cerebellar information processing. Nat Neurosci 3:1205–1211
Moore JW, Choi JS (1997) Conditioned response timing and integration in the cerebellum. Learn Mem 4:116–129
Neidhard-Doll AT, Phillips CA, Repperger DW, Reynolds DB (2004) Biomimetic model of skeletal muscle isometric contraction: II. A phenomenological model of the skeletal muscle excitation-contraction coupling process. Comput Biol Med 34:323–344
Prince JH (1964) The rabbit in eye research. Charles C. Thomas, Springfield, Il
Sanchez-Campusano R, Delgado-García JM, Gruart A (2003) A phenomenological model for the neuromuscular control of reflex and learned eyelid responses. Society for Neuroscience Abstracts Program No:78.72
Shadmehr R, Arbib MA (1992) A mathematical analysis of the force-stiffness characteristics of muscles in control of a single joint system. Biol Cybern 66:463–477
Shames DM, Baker AJ, Weiner MW, Camacho SA (1996) Ca2+-force relationship of frog skeletal muscle: a dynamics model for parameter estimation. Am J Physiol 271 (Cell Physiol 40):C2061–C2071
Stein RB, Wong EY-M (1974) Analysis of models for the activation and contraction of muscle. J Theor Biol 46:307–327
Thompson RF (1983) Neuronal substrates of simple associative learning: classical conditioning. Trends Neurosci 6:270–275
Trigo JA, Gruart A, Delgado-García JM (1999) Discharge profiles of abducens, accessory abducens, and orbicularis oculi motoneurons during reflex and conditioned blinks in alert cats. J Neurophysiol 81:1666–1684
Watanabe T, Futami R, Hoshimiya N, Handa Y (1999) An approach to a muscle model with a stimulus frequency–force relationship for FES applications. IEEE Trans Rehabil Eng 7:12–18
Zahalak GI, Motabarzadeh I (1997) A re-examination of calcium activation in the Huxley cross-bridge model. J Biomech Eng 119:20–29
Zhou BH, Baratta R, Solomonow M (1987) Manipulation of muscle force with various firing rate and recruitment control strategies. IEEE Trans Biomed Eng 34:128–139
Author information
Authors and Affiliations
Corresponding author
Additional information
Codes for all figures are available from http://www.neuralalgorithms.com (and also http://www.lepora.com) or by email from N. Lepora.
Rights and permissions
About this article
Cite this article
Mavritsaki, E., Lepora, N., Porrill, J. et al. Response linearity determined by recruitment strategy in detailed model of nictitating membrane control. Biol Cybern 96, 39–57 (2007). https://doi.org/10.1007/s00422-006-0105-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00422-006-0105-5