Special Lectures BERGER LECTURE
Mechanisms underlying synapUc plasticity in neocortex
Tadaharu Tsumoto. Department of Neurophysiology, Biomedical Research Center, Osaka University Medical School Functional properties of neocortical neurons and thus certain functions of the neocortex are modifiable during the "critical period" of postnatal development. This type of neuronal plasticity was first demonstrated by Hubel and Wiesel in 1963 in the visual cortex of young kittens with the monocular visual deprivation paradigm. Since then, the number of studies have suggested that a use-dependent, long-term alteration of synaptic efficacy may underlie such cortical plasticity. In 1979, we reported that the efficacy of synapses in kitten visual cortex can be potentiated or depressed for long time following repetitive afferent stimulation, a p h e n o m e n o n similar to that called long-term potentiation (LTP) or depression (LTD) in the hippocampus, and suggested that such a LTP/LTD-like p h e n o m e n o n may underlie plasticity of neocortical function. Then, a question arose: what determines the direction of change of synaptic efficacy, such as LTP or LTD. Subsequently, the following hypothesis was put forward to this question: the extent to which the concentration of postsynaptic Ca -'+ is increased during synaptic inputs determines the direction of changes. For example, the high increase beyond a certain threshold may activate Ca2+/calmodulin-dependent protein kinase !1 ~o as to lead to the induction of LTP while the lower rise below the threshold may activate Ca2+/calmodulin-dependent protein phosphatase (calcineurin) to lead to the induction of LTD. We tested this possibility, using the Ca2+-imaging and other techniques m visual cortical slices of young rats. The results so far obtained seem essentially consistent with this hypothesis.
Ion channels and nerve conduction Stephen G. Waxman. Dept. of Neurology, Yale School of Medicine, New Haven, CT06510 and PV.4/EPVA Neuroscience Research Ctr, VA Hospital, West Haven, CT 06516 Although Adrian recognized the all-or-none character of the action potential and its crucial function in the encoding of neural information, the molecular basis for action potential conduction was not elucidated until several decades after Adrian's studies and is still being refined at the present time. This lecture will review recent progress in our understanding of the role of ion channcls and related molecules in the conduction of nerve impulses. Much of this newer information has important implications for neurology and clinical electrophysiology. This lecture will discuss the following: 1. In mammalian myelinated fibers, various types of ion channels are not distributed at random but, on the contrary, have a highly ordered distribution. For example, Na + and fast K + channels have a complementary distribution, with Na + channels clustered in high
density in the axon membrane at the node of Ranvier, and fast K + channels located in the paranodal/internodal axon m e m b r a n e under the myelin sheath. 2. Several types of K + channels are present in mammalian myelinated axons. In addition to fast K + channels, slow K + channels are present (in part, within the nodal membrane) and serve to modulate high-frequency firing. 3. Different types of Na + channels are present in different types of axons. An example is provided by cutaneous sensory axons, which possess slowly-activating and -inactivating Na + channels, in contrast to muscle afferent axons which express rapidly-activating and -inactivating Na + channels. The presence of different types of Na + channels, in different types of axons, may underly specific affection of various axon types in peripheral neuropathies, and may provide an opportunity for pharmacologic manipulation of specific types of axons. 4. Na + channels are present in both axons and associated myelin-forming ceils. Schwann cells, as well as astrocytes, express Na + channels (both c~ and /3 subunits). The presence of these channels in glial cells has important pathophysiological, as well as physiological, implications. As we move to a molecular and mechanistic level, Adrian's elucidation of the action potential will probably become increasingly relevant to neurological disease.
Muscle spindles and fusimotor system in man
KarI-Erik Hagbarth. Department of Clinical Neurophysiology, Academic Hospital, Uppsala, Sweden Special neurographic techniques, developed during the last decades, allow documentation of afferent muscle spindle activity as well in freely moving animals as during different types of motor acts in co-operative h u m a n subjects. In many respects human muscle spindle behaviour, as documented in microneurographic recordings, is similar to the spindle behaviour observed in freely moving cats. However, there is one important disparity between the human and animal data. Whereas animal experiments provide evidence for flexible, set-dependent variations in the fusimotor outflow to the spindles, evidence for such flexibility (with signs of or-)/dissociation) has been very difficult to find in the human-based studies. The reasons for this disparity are still obscure, but at least some of the seemingly conflicting results may be explained by the so-called 'thixotropic' mechanical properties of both extra- and intrafusal muscle fibres. As a result of these properties muscle spindle output is strongly affected by the movement and contraction history of the parent muscle. Both in animal- and in human-based studies misinterpretations concerning fusimotor control mechanisms can easily arise if proper account is not taken to these history-dependent variations in muscle fibre biomechanics. Muscle fatigue is another factor to be considered in this context. The muscle spindle response to a given fusimotor output may change during muscle fatigue and give a false impression of ~x-)/ dissociation.