Nervous control (15/10/13 lecture) Nervous control is primarily involved in rapid movement, but also in collecting, processing and responding to information from the environment. The brain is also an integrating centre for homeostasis, allowing it to be a part of longer term control too. The ‘information’ propagated through the nervous system can take several forms: action potentials, neurotransmitter release, and graded potentials. Many variations may occur in a reflex arc, which allows for control of these signals. Ion channels are important in the nervous system as they allow for the generation of action potentials (depolarisation) when a change in the resting membrane potential or neurotransmitter binding occurs. There are also mechanically gated ion channels activated by pressure/distortion of membrane. Nervous system divisions: The main divisions are the central and peripheral nervous systems. The CNS is divided into the brain and spinal cord. The PNS is divided into motor neurons and sensory neurons. The motor neurons are divided into the somatic and autonomic nervous systems (though the ANS has sensory neurons too). The ANS is divided into the sympathetic (fight or flight) and parasympathetic (maintenance). Somatic motor neurons are monosynaptic, heavily myelinated cholinergic neurons; their long axons extend from the CNS to the effector with no ganglia (alpha-motorneurons) for fast propagation. Autonomic motor pathways consist of two neurons: the pre-ganglionic, heavily myelinated cholinergic neuron which is short and extends from the CNS to a peripheral ganglion; and the post-ganglionic unmyelinated, adrenergic, longer neuron which extends to an effector organ from the ganglion. Somatic efferent pathway: Sensory information arrives through dorsal root (where cell bodies of sensory neurons are) to dorsal horn of spinal cord → Information travels through an interneuron → An α-motoneuron is stimulated in the ventral horn and the action potential is propagated through the ventral root to the effector organ e.g. skeletal muscle. Autonomic efferent pathway: Sensory information arrives through dorsal root ganglion to dorsal horn of spinal cord → Information travels through an interneuron → A pre-ganglionic neuron extends from the CNS to the white ramus →This synapses with the unmyelinated grey ramus in a peripheral ganglion using ACh and a nicotinic receptor → The post-ganglionic neuron extends to the effector organ and stimulates it. The peripheral sympathetic chain ganglia are connected, which allows for communication and the possibility for the generation of a systemic/widespread effect. At the target tissue: Sympathetic cAMP signal transduction: adrenaline/noradrenaline binds to α2 or β-adrenoceptor → binding causes conformational change which separates G protein complex (α separates from βγ) (α2-adrenoceptor linked with G-inhibitory protein complex; β-adrenoceptor linked with G-stimulatory complex) → The α subunit migrates through the membrane and binds to adenylate cyclase → Giα downregulates conversion of ATP to cAMP whereas Gsα upregulates it → cAMP phosphorylates protein kinase A →protein kinase A phosphorylates another protein e.g. myosin light chain phosphatase →cellular response e.g. dephosphorylation of myosin light chains and smooth muscle relaxation. Sympathetic phospholipase C signal transduction: adrenaline/noradrenaline binds to α1-adrenoceptor → the Gs complex is separated into its α and βγ subunits → the α subunit migrates through the membrane and binds to amplifier enzyme phospholipase C, activating it → phospholipase C converts membrane proteins (phosphatidylinositol bisphosphate – PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3), secondary messengers → DAG activates protein kinase C which phosphorylates proteins to generate a response and propagate the signal → IP3 migrates from the membrane to the endoplasmic/sarcoplasmic reticulum and binds to a Ca2+ channel, opening it → in smooth muscle, the response is that Ca2+ binds to calmodulin which activates myosin light chain kinase, phosphorylating myosin light chains, and causing smooth muscle cell contraction. Nicotinic ACh receptor: Na+ channel. Muscarinic ACh receptor: G-protein associated/K+ channel. A reflex is an automated patterned response to sensory stimuli: stimulus → sensory receptor → sensory afferent neuron → CNS integration → efferent motor neuron → effector → response → feedback effect on stimulus. Although a monosynaptic neural reflex may appear to have minimal modulation, there are 2-3000 other synapses attached to the α-motoneuron which are stimulatory/inhibitory and dictate whether it fires – here is modulation. Ways of classifying neural reflexes: Effector division Integration site Neurons in pathway Origin Somatic (movement in external world) Autonomic (motor activity in internal world) Spinal (‘low’ level, relatively simple) Brain (‘high’ level, more complex) Mono-synaptic Poly-synaptic (all autonomic reflexes) Innate (knee-jerk reflex, pupillary reflex) Learned (Pavlovian, walking) Reflexes Autonomic/visceral reflexes are usually involved in regulating internal organs (e.g. moving or limiting movement of products in hollow organs) and are integrated in the spinal cord and lower (subconscious) brain. However, they can be modulated by higher (conscious) levels. Typically: Stimulus → sensory receptor in viscera → impulse in visceral (sensory) fibre →travels to dorsal root ganglion then to dorsal horn → integrated in the spinal cord, perhaps by the preganglionic neuron → impulse travels out of ventral horn along a preganglionic axon → it reaches an autonomic ganglion and synapses with a ganglionic neuron → these exist as chain ganglia so there can be divergence of response → impulse travels along the postganglionic axon to the visceral effector →a response occurs → there is feedback to the CNS as to the status of the stimulus. The pupillary light reflex: constriction is parasympathetic, relaxation is sympathetic. Light hits the photoreceptors in the retina in one or both eyes → The pupillary reflex is activated and signals travel through the optic nerve to the thalamus, then to the midbrain → Signals then continue to travel through the efferent, parasympathetic neurons (if too much light, sympathetic if too little) running through cranial nerve III (the oculomotor nerve) to constrict the pupils in both eyes via circular pupillary muscles in the iris or dilate the pupils in both eyes via contraction of radial muscles lying perpendicular to the circular muscles → Less light hits the retina in both eyes (the consensual reflex) or more light hits it → Signals return to the thalamus that the light level is appropriate → Contraction of the pupillary muscles in the iris stops at the optimal diameter for the pupils and dilatory signals are inhibited, or contraction of the radial muscles stops at the optimal diameter for the pupils and constrictive signals are inhibited. The baroreceptor reflex: baroreceptors in the aortic arch and the internal carotid arteries are sensitive to stretch. The receptors are active during normal pressure and sending constant impulses to the medulla regarding the level of stretch, the heart rate, and the rate of change in pressure. When arterial pressure changes, arterial walls are subjected to more or less stretch, and the sensory nerves coming from the carotid sinus (sinus nerve) and from the aortic arch (depressor nerve) become more or less active and send more or fewer impulses. Upon receiving more or fewer impulses from the baroreceptors, the cardiovascular centres respond by exciting sympathetic and inhibiting parasympathetic nerves (if BP has dropped) or exciting parasympathetic and inhibiting sympathetic nerves (if BP has risen). This either results in increased cardiac output, increased constriction of arterioles, and increased constriction of veins (if BP has dropped), or a decrease in these factors (if BP has risen). The hypothalamus is the main integration centre of ANS activity, but at the conscious level there can be limbic lobe and cerebral cortex (frontal lobe) control, and control from the lower levels of the reticular formation of the brain stem, and from the spinal cord. Somatic reflexes involve the skeletal muscles as effectors, but sensors can classically be muscle spindles (in stretch reflex), Golgi tendon organs (in autogenic inhibition), or ‘pain’ receptors (in flexion). Proprioceptors include muscle spindles (which sense stretch), Golgi tendon organs (which sense force) and joint receptors (which sense pressure, interpreted as position). Muscle spindles are made up of small muscle fibres, the centre portions of which have no contractile proteins as there are nerve endings there. Golgi tendon organs consist of sensory nerve endings interwoven among collagen fibres, and link the muscle and the tendon. In muscle spindle innervation, there is α-γ co-activation. This allows for greater control over movements. The muscle spindles may send efferent impulses via sensory nerves to the spinal cord in accordance with skeletal muscle movement, which stimulates γ-neurons, resulting in the contraction of the intrafusal muscle fibres of the spindle. This contraction lengthens the non-contractile spindle, resulting in γ-neuron activity. This is again integrated in the spinal cord, and impulses may now be sent along α-motoneurons, which cause skeletal muscle contraction. An example of this may be in being handed a heavy tray. A myotactic unit consists of all pathways controlling a joint (all nerves, receptors, and muscles). Renshaw cells are interneurons that synapse with recurrent branches (those that synapse in the CNS) of α-motoneurons. They receive excitatory inputs, and make inhibitory synapses upon the same motor neurons which can limit motor neuron firing to dampen/reduce reflexes and prevent them becoming too aggressive. Synergist muscles may also be excited by spindle afferents making excitatory monosynaptic connections, and antagonist muscles are inhibited with inhibitory synapses on motor neurons in reciprocal inhibition. The Golgi tendon reflex prevents tendons from becoming overstretched. When the tendon is stretched by muscle contraction, the 1b sensory nerve is are compressed by the collagen in the Golgi tendon organ and afferent neurons integrate via an inhibitory interneuron and inhibit further motor neuron excitation, inhibiting contraction and preventing damage. The Golgi tendon organ also makes an excitatory synapse on another interneuron to make an inhibitory synapse on synergist muscle motor neurons. Further, it makes an excitatory synapse on an interneuron which makes an excitatory synapse on motor neurons to antagonist muscles, causing them to contract so that the original muscle is not only relaxed but stretched out. The flexor reflex: a painful stimulus activates nociceptors → the primary sensory neuron enters the spinal cord and diverges → one collateral activates ascending pathways for sensation (pain) and postural adjustment → this results in a withdrawal reflex pulling the limb away from the painful stimulus → the other activates a crossed extensor reflex which supports the body as the weight shifts away from the painful stimulus (e.g. stand on a pin, and the opposite leg’s extensors (posterior quadriceps) contract). In reflexive movement, there is predominately spinal integration, and some input to the brain (e.g. you can resist dropping something important when you stand on something sharp). However, in postural reflexes, there is cerebellum integration to maintain balance, and input to the cortex, which is where movement can be consciously influenced. In postural reflexes, there is feedforward stimulation, typically in expectation of a threat. As the brain initiates movement, there is feedforward activity which adjusts the posture before or as the body moves. There is also feedback after unanticipated postural disturbance, so that posture can be appropriately adjusted once more. Rhythmic movements are learned, for example walking and driving. These are initiated in the cortex, at a conscious level. However, after this the control becomes subconscious and there are ‘central pattern generators’ in the spine which maintain motion. These combine both voluntary and reflexive movements. The corticospinal tract consists of the cortex (e.g. primary motor cortex), the medulla oblongata, and the spinal cord, so that movements may be initiated and then maintained. The cortex is ‘at the top’ of several CNS integration sites. This is generally considered voluntary as it is ‘conscious’, but parts can become involuntary – muscle memory, for example walking and driving. So is this voluntary, or a complicated reflex? Voluntary movement: sensory input from the sensory and motor cortices is received by the prefrontal cortex nd motor association areas → these impulses are transmitted through the basal nuclei and the thalamus and back to the prefrontal cortex and motor association areas (‘planning and decision making’) →impulses travel back to the motor cortex and then to the cerebellum for coordination and timing → impulses travel to the brain stem for execution via the spinal cord and somatic motor nerves – influence on posture, balance and gait → sensory receptors transmit impulses to the spinal cord, cerebellum and sensory cortex as continuous feedback.