Lecture11 - BioNB222 Cornell University Spring 2008 Ronald...

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BioNB222 Spring 2008 Cornell University Ronald Harris-Warrick 1 Lecture 11. Neuromodulation Reading Assignment Purves et al., Chapter 7. Summary: The slow actions of neuromodulators allow neurons and their synapses to have variable properties rather than fixed properties. This helps constitute the basis for behavioral flexibility in our everyday movements. Any neurotransmitter can act as a neuromodulator by binding to a modulatory receptor, which evokes effects that are slow, subtle, biochemically complex and use physiological mechanisms that are quite different from fast transmitter actions. The typical modulatory receptor is a G-protein-coupled receptor, or metabotropic receptor: acting through the intermediary G proteins, they trigger a cascade of biochemical events in the neuron that last far longer and spread far wider than a standard transmitter action. Physiologically, modulators canincrease or decrease the strength of synapses. They can gind to receptors on the pre-synaptic terminal and alter the amount of neurotransmitter released in response to an action potential, or they can bind post-synaptically to alter the response to the neurotransmitter. Modulators can also change the firing properties of neurons, evoking oscillatory behavior, bistability, varied post-inhibitory rebound, etc. Neuromodulators evoke these changes by altering the activity of leak channels as well as voltage-sensitive ion channels. Learning Objectives 1. To know the basic characteristics that distinguish neuromodulator action from neurotransmitter actions. 2. To understand the basics of signal transduction, the biochemical steps by which binding of the modulator to its receptor evokes broad and varied changes in enzyme and channel activity in the cell. 3. To understand the physiological mechanisms of modulator action, including their ability to affect the properties of voltage-dependent ion channels, and to act on leak channels. 4. To understand how a conductance decrease PSP enhances the excitability of the neuron 5. To see how these modulatory actions explain how we can suppress our perception of painful stimuli when it is necessary for our survival. Lecture Outline Neurons and synapses exhibit remarkable plasticity and flexibility in their properties. Part of this flexibility is intrinsic to the neuron or synapse, for example, synaptic facilitation and depression, as described in the last lecture.
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2 However, much of it is due to extrinsic modulation, that is, the effects of synaptic inputs. Even synapses themselves can be the target of synaptic modulation! A. Neuromodulators Neuromodulatory synapses change the strength of other synapses and change the firing properties of other neurons. These actions can be mediated by a number of different transmitters: monoamines (dopamine, norepinephrine, serotonin) and peptides (endorphins, substance P, etc.) nearly always act as modulators, but any transmitter can have a modulatory action if it binds to the right receptor. As usual,
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Lecture11 - BioNB222 Cornell University Spring 2008 Ronald...

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