2h Neuroscience with Pharmacology Functions and Mechanisms of Reflexes Neuroscience is studied at many different levels: from brain, to system, network, neurone, synapse, and molecule... Top Up Down René Descartes Cogito, ergo sum ( I think therefore I am ) Bottom Santiago Ramon y Cajal (ca 1900) : the Neurone Doctrine Neurones in the Brainbow transgenic mouse brain are multicoloured ca. 1900: Sherrington proposes the concept of the synapse So far as our present knowledge goes we are led to think that the tip of the [axon s] arborescence is not continuous with but merely in contact with the substance of the dendrite or cell body on which it impinges. Such a special connection of one nerve cell with another might be called a synapse. C.S. Sherrington; in Foster,M. A Textbook of Physiology. 7th edn. 1897 συν together απτειν to clasp 1
The brain is mostly synapses (1000 times more synapses than neurones) Cerebral cortex (rat) 1 µm Integrated Circuit Number of Transistors in Intel Pentium Dual Core microprocessor : 1.67x 108 Number of Neurones in 1 Human Brain : ~ 1010 1012 Number of Synaptic Connections in 1 Human Brain : ~ 1015 Human Population of Planet Earth: 6.98 x 109 Prof Ribchester Neuroscience is studied at many different levels: from brain, to system, network, neurone, synapse, and molecule... Top Middle Bottom 2
Dorsal (Posterior) Afferent Efferent Ventral (Anterior) Let s build a brain, connecting input and output neurones. A monosynaptic reflex Initiation Conduction Transmission End effect Muscle spindles monitor muscle stretch/length Yabushita et al (2006) J DENTAL RES, Vol. 85, No. 9, 849853 (2006) http://upload.wikimedia.org/wikipedia/commons/6/67/spindle.gif http://content.answers.com/main/content/img/oxford/oxford_food_fitness/0198631472.muscle.1.jpg 3
Glutamate and ACh are neurotransmitters in the monosynaptic stretch reflex glutamate Sensory receptors in skeletal muscle. Skeletal (Extrafusal) muscle Extrafusal (skeletal) muscle fiber Muscle spindle Intrafusal muscle fibers Nuclear bag fiber Nuclear chain fiber Equatorial region Polar regions Muscle spindle primary afferent (Ia) Ia facilitatory reflex connections Muscle spindle secondary afferent (II) Golgi tendon organ (GTO) GTO primary afferent (Ib) Ib inhibitory reflex connections Inhibitory interneuron Dorsal (Posterior) spinocerebellar tract Ventral (Anterior) spinocerebellar tract Alpha lower motor neuron Dynamic gamma lower motor neuron Static gamma lower motor neuron Acetylcholine EPSP http://www.csus.edu/indiv/m/mckeoughd/aanatomyrev/mm_recept/mmreceptors.htm Charles Sherrington From : Sherrington,C.S.(1906/47). The integrative action of the nervous system. Cambridge University Press Reciprocal Inhibition: A disynaptic reflex Flexion withdrawal reflex Crossed Extension reflex http://www.colorado.edu/intphys/class/iphy3730/image/figure524.jpg 4
Synaptic potentials underlie reflex excitation and inhibition EPSP / /.increasing the complexity: GABA glutamate Acetylcholine Glycine John Eccles IPSP Acetylcholine Input Integration Output Dendrites Soma Axon Hillock Orthodromic conduction Initial Segment Myelinated axon Spatial summation Temporal summation 5
Synaptic facilitation http://snnap.uth.tmc.edu/images/examples/psm_fcln.gif Synaptic depression http://snnap.uth.tmc.edu/images/examples/psm_deprsn.gif Axons do not regenerate after spinal cord transection Stem cell therapies may facilitate spinal cord regeneration The Final Common Path. Raisman G. Olfactory ensheathing cells and repair of brain and spinal cord injuries. Cloning Stem Cells. 2004;6(4):3648. Li, Field & Raisman (2005) Science 26 September 1997:Vol. 277. no. 5334, pp. 2000 2002 6
Specialised physiotherapies may enhance ( train ) the function of spinal reflex circuits and synapses.increasing.add plasticity the complexity: / / Adaptive Input Integration Output Summary 1. Neuroscience is studied at many levels: from clinical to basic; from systems to cells to molecules 2. Complex neural functions arise from the ways neurones are connected at synapses, in specific neural circuits 3. The monosynaptic stretch reflex (kneejerk reflex) is an example of the simplest neural circuit; it involves only two neurones: a primary afferent sensory neurone and an efferent motor neurone 4. Information is encoded in the pattern and frequency of action potentials and in the size and shape of synaptic potentials. 5. EPSPs and IPSPs mediate excitatory and inhibitory synaptic transmission respectively, using distinct neurotransmitters (e.g. glutamate, excitatory; GABA, inhibitory) and specific receptors. 6. Multisynaptic excitatory and inhibitory spinal reflexes are integrated to generate complex motor patterns, refined by learning ( plasticity ) 7. Engineering recovery from spinal injury requires reconnection of injured descending motor pathways to intact spinal reflex circuits 7