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Neuroscience Journal Club 19 February 2008 Henry Lester

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  1. Neuroscience Journal Club 19 February 2008 Henry Lester

  2. H Alle and J R. P. Geiger (2006) Combined Analog and Action Potential Coding in Hippocampal Mossy Fibers Science 311: 1290 Y Shu, A Hasenstaub, A Duque, Y Yu & D. A. McCormick (2006). Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential Nature 441: 761 and PNAS, 2007 M. H. P. Kole, J. J. Letzkus, G. J. Stuart (2007) Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy Neuron, 2007 Hideki Kawai, Ronit Lazar & Raju Metherate (2007) Nicotinic control of axon excitability regulates thalamocortical transmission Nature Neurosci 10, 1168

  3. Classical studies (Katz & Miledi, squid synapse) show . . . Presynaptic voltage-dependent Ca channels are the major source of Ca influx leading to transmitter release. These Ca channels do not inactivate strongly on a ms time scale. On a ms time scale, the Ca sensors seem to integrate Ca influx. In nonsaturating regimes, release depends strongly on the Ca influx—probably to the 3rd or 4th power. Therefore transmitter release depends strongly on the duration of the presynaptic AP.

  4. The prevailing mode to encode information in the mammalian central nervous system is to convert an analog signal resulting from graded synaptic inputs into patterns of action potentials, which are transmitted as all-or-none signals along the axons. By contrast, in primary sensory systems and central neural circuits of small invertebrates, analog signals are used directly to transmit information. In many brain regions the axonal distances from the cell body to a large fraction of the corresponding presynaptic boutons are rather short and somatic subthreshold signals can be large in amplitude. The question arises whether analog axonal signaling contributes to information transmission in the mammalian brain. Paraphrased from Alle & Geiger, intro

  5. Caltech Neuroscience Journal Club, February 1986 Presented by Jeanne Nerbonne O Belluzi, O Sacchi, E. Wanke (1985). A fast transient outward current in the rat sympathetic neurone studied under voltage-clamp conditions. J Physiol. 358:91-108

  6. The Basic Phenomenon: Depolarizing the Presynaptic Soma  Larger EPSP Yu et al, Figure 1

  7. The mechanism: Changes in somatic membrane potential affect amplitude & duration of somatic and axonal action potentials Yu et al, Figure 3

  8. Spontaneous barrages of synaptic activity propagate down the axon Yu et al, Figure 4

  9. EPreSPs: recorded in mossy fiber boutons; generated upstream of the CA3 region. Alle & Geiger Figs 1 & 2

  10. Electrotonic propagation of somatic depolarizations underlies EPreSPs. Alle & Geiger Fig 3

  11. Dual pre- & postsynaptic V-clamp: nerve terminal depolarizations do increase EPSCs Alle & Geiger Fig 3

  12. One can patch onto 3-4 μm blebs in cut-off axons; this is useful Kole et al, Fig. 1

  13. More bleb recordings

  14. Kv1.2* channels appear to control AP waveform α-DTX specifically blocks Kv1.1*, 1.2*, or 1.6* channels; low doses of 4-APblock less specifically. Tityustoxin-Kα, which is relativelyspecific for K+ channels containing Kv1.2 subunits stronglyblocked the slowly inactivating K+ current in cortical axons,whereas dendrotoxin-K, which is relatively specific for Kv1.1subunits, exhibited only marginal effects.  Kv1.2* channels arethe mediators of the D-current responsible for axonal spikerepolarization. Immunocytochemical studies reveal the prominentexpression of Kv 1.2 channels in axons and axonal terminal fieldsthroughout the brain. In the neocortex, Kv1.2is of particularly high density in the more distal portionsof the axon initial segment of cortical pyramidal cells. Yu et al PNAS 2007

  15. More dual recordings

  16. Nicotine enhances success rate for thalamocortical EPSCs . . . Kawai et al

  17. . . . because nicotine enhances success rate for thalamocortical axonal transmission Subcortical white matter axons Local nicotine perfusion STR =superior thalamic radiation Kawai et al

  18. Chronic nicotine: increases perforant path a4* nicotinic receptor fluorescence ~ 2-fold Alveus Py Or Rad • TV Bliss, T Lömo (1973) • Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. • J Physiol. 232:331-56. LMol 200 mm Temperoammonic Path Medial Perforant Path Nashmi et al, 2007

  19. Acute Nicotine Acute Saline 80 min 10 min 80 min 10 min Chronic Chronic 1 mV Saline Saline 10 ms 0.5 mV 0.5 mV 10 ms 5 ms Nicotine 1mV Nicotine 1 mV 10 ms 10 ms Simple model for cognitive sensitization: chronic nicotine + acute nicotine lowers the threshold for perforant pathway LTP Acute Nicotine Acute Saline Chronic Nicotine Acute Nashmi et al, 2007 Chronic Chronic