Neuroscience Colloquia, New York University
Additional Information, Fall 1997

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Speaker: Erin Schuman
Title: Diffusible Signals and Hippocampal Synaptic Plasticity
Abstract: Information can be stored in the adult nervous system by changing the propertiesof synapses. During the neuronal development and synaptogenesis the neurotrophin family of growth factors promote the growth and survival of neurons and synapses. We have explored whether the neurotrophins may play a similar role in modulating synapses in the adult hippocampus. We have found that the neurotrophins can cause long-lasting synaptic plasticity that relies on the local synthesis of proteins, likely in the dendrites. Moreover, in examining the role of neurotrophins in synaptically-induced plasticity, we have found that the specific temporal pattern of synaptic inputs determines whether neurotrophin signaling is important. During which temporal window do neurotrophins operate to influence synaptic plasticity? It appears that neurotrophin signaling is required for up to an hour following the inducing stimulus. The ramifications of neurotrophin signaling and stimulation of protein synthesis will also be discussed.
Related
articles:
  • Kang, H., Welcher, A. and Schuman, E.M. (1997). Neurotrophins and time: different roles for TrkB signaling in hippocampal long-term potentiation,, Neuron, 19, 653-664.
  • Schuman, E.M. (1997). Synapse specificity and long-term information storage. Neuron, 18, 339-342.
  • Kang, H. and Schuman, E.M. (1996). A requirement for local protein synthesis in neurotrophin-induced synaptic plasticity, Science, 273, 1402-1406.
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    Speaker: Eric R. Kandel
    Title: Genes, Synapses and Long Term Memory
    Abstract: Cognitive psychological studies have shown that there are at least two distinct types of learning: memory about people, places, and things (explicit or declarative forms of learning), and learning about motor skills and perceptual strategies (implicit or procedural forms of learning). These two forms of learning have been localized to different neural systems within the brain. Explicit learning requires regions within the temporal lobe of the cerebral cortex including the hippocampus, whereas implicit learning involves the specific sensory and motor systems recruited for the particular task. As a result, implicit learning has been studied in a variety of simple reflex systems, including those of invertebrates such as Aplysia and Drosophila. By contrast, explicit forms of learning can best (and perhaps only) be studied in mammals. To what degree do these two major learning processes share common molecular steps? One clue to shared mechanisms comes from the study of memory storage, the retention of information acquired through learning. Results from Aplysia, Drosophila, and mice suggest that both forms of memory seem to share components of a common molecular switch to convert short-term into long-term memory. In Aplysia and Drosophila, where the data are most complete, this switch involves the coordinated expression of the cyclic AMP responsive element binding protein transactivator (CREB-1) (and at least two other activators), and the concomitant relief of repression by CREB-2. Removal of the repressor lowers the threshold for memory storage and leads to immediate long-term memory.
    Speaker: David Ferster
    Title: Assembly of receptive fields in cat visual cortex
    Related
    articles:
  • Jagadeesh, B., Wheat, H.S. & Ferster, D. (1993) Linearity of summation of synaptic potentials underlying direction selectivity in simple cells of the cat visual cortex. Science 262:1901-904.
  • Ferster, D. Chung, S. and Wheat, H. (1996) Orientation selectivity of synaptic input from the lateral geniculate nucleus to simple cells of the cat visual cortex. Nature 380: 249-252.
  • Carandini, M. and Ferster, D. (1997) A tonic hyperpolarization underlying contrast adaptation in cat visual cortex. Science 276:949-952.
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    Speaker: David McCormick
    Title: Cellular mechanisms of network function
    in the mammalian visual system in sleep and waking
    Abstract: Synchronized oscillations are a common product of mammalian thalamocortical networks during slow wave sleep, attentiveness, and generalized seizures. Of these synchronized oscillations, spindle waves are the best understood at both the cellular and network level. Spindle waves are generated in the thalamus during early stages of sleep and propagate to the cerebral cortex where they are recorded in the electroencephalogram as a 7-14 Hz oscillation that waxes-and-wanes over a 1-4 second period and are followed by a refractory period of several seconds. Spindle waves may be perverted into abnormally strong oscillations during absence (petit mal) seizures of generalized epilepsy.

    The ferret dorsal lateral geniculate nucleus (LGNd) maintained as slices in vitro generate spontaneous spindle waves that are very similar to those recorded in vivo. We obtained data suggesting that spindle waves are generated largely through a cyclical interaction between populations of thalamocortical and thalamic reticular or perigeniculate (PGN) neurons involving both the intrinsic membrane properties of these neurons and their anatomical interconnections (Bal & al., J. Physiol. 483.3: 641-685, 1995). Reticular thalamic and thalamocortical neurons possess ionic currents that allow these cells to generate either rhythmic burst firing at rest or single spike activity upon depolarization. When anatomical interactions between PGN GABAergic and LGNd thalamocortical neurons are preserved, such as in slices of the ferret LGNd in vitro, spindle waves are produced as a sequence of inhibition in thalamocortical cells followed by rebound bursts of action potentials. Burst firing in relay neurons then excites PGN neurons, thereby completing the loop and starting the next cycle of oscillation. Simultaneously, PGN neurons regulates each others firing through lateral inhibitory interactions (Sanchez-Vives et al., submitted, 1997).

    During normal spindle wave generation the IPSPs occurring in relay neurons are mediated through the activation of GABAA receptors. However, when GABAA receptors are blocked with bicuculline, the network generates an enhanced but slowed oscillation (2-4 Hz) that resembles in many aspects the activity of thalamic networks during the generation of an absence seizure. In relay neurons, this slowed oscillation is associated with large, slow IPSPs mediated through the activation of GABAB receptors. These large IPSPs greatly enhance rebound Ca2+ spikes and associated bursts of action potentials resulting in strong excitation of PGN cells. Interestingly, block of GABAB receptors abolished this "seizure-like" activity, but not normal spindle waves, suggesting that GABAB antagonists may be useful in the treatment of absence epilepsy.=20 What stops thalamic synchronized oscillations and generates a refractory period is associated with a long-lasting afterdepolarization (ADP) in thalamocortical cells and decreased ability to generate rebound bursts following monosynaptic inhibition from PGN neurons. This slow ADP was reversibly blocked by extracellular local application of cesium, a specific blocker of the hyperpolarization-activated cation current Ih. Bath application of Cesium suppressed the refractory period and transformed both spindle and bicuculline-induced slow oscillation into continuous network oscillations (Bal & McCormick, Neuron 17: 297-308,1996). These results were recently confirmed by the use of ZD 7288, another specific blocker of Ih (L=FCthi, Bal and McCormick, unpublished observations). We propose that the afterdepolarization is generated through a persistent activation of Ih resulting from rhythmic barrages of IPSPs and the generation of rebound Ca2+ spikes and that the generation of this ADP in thalamocortical neurons plays a crucial role in the cessation of normal or abnormal thalamic synchronized oscillations and the generation of a refractory period.

    Related
    articles:
  • McCormick, D.A., and Bal, T. (1997) Sleep and Arousal: Thalamocortical mechanisms. Ann. Rev. Neurosci. 20:185-215.
  • Lee, K., and McCormick, D.A. (1996) Abolition of spindle oscillations by serotonin and norepinephrine in the ferret lateral geniculate and perigeniculate nuclei in vitro. Neuron, 17: 309-321.
  • Bal, T., and McCormick, D.A. (1996) What stops synchronized thalamocortical oscillations? Neuron, 17: 297-308.
  • Gray, C.M. and McCormick, D.A. (1996) Chattering cells: Superficial pyramidal neurons contributing to the generation of synchronous oscillations in the visual cortex. Science 274: 109-113.
    		•
    Speaker: Dan Margoliash
    Title: Functional organization and neural codes in the bird song system
    Abstract: This paper reviews the organization of the forebrain nuclei of the avian song system. Particular emphasis is placed on recent physiological recordings from awake behaving adult birds while they sing, call, and listen to broadcast of acoustic stimuli. The neurons in the descending motor pathway (HVc and RA) are organized in a hierarchical arrangement of temporal units of song production, with HVc neurons representing syllables and RA neurons representing notes. The nuclei Uva and NIf, which are afferent to HVc, may help organize syllables into larger units of vocalization. HVc and RA are also active during production of all calls. The patterns of activity associated with calls differ between learned calls and those that are innately-specified, and give insight into the interactions between the forebrain and midbrain during calling, as well as into the evolutionary origins of the song system. Neurons in area X, the first part of the anterior forebrain pathway leading from HVc to RA, are also active during singing. Many HVc neurons are also auditory, exhibiting selectivity for learned acoustic parameters of the individual bird=B9s own song (BOS). Similar auditory responses are also observed in RA and area X in anesthetized birds. In contrast to HVc, however, auditory responses in RA are very weak or absent in awake birds under our experimental paradigm, but are uncovered when birds are anesthetized. Thus, the sensory roles of both pathways beyond HVc in adult birds is under review. In particular, theories hypothesizing a role for the descending motor pathway (RA and below) in adult song perception do not appear to obtain. The data also suggest that the anterior forebrain pathway has a greater motor role than previously considered. We suggest that a major role of the anterior forebrain pathway is to resolve the timing mismatch between motor program readout and sensory feedback, thereby facilitating motor programming during birdsong learning. Pathways afferent to HVc may participate more in sensory acquisition and sensorimotor learning during song development than is commonly assumed.
    Related
    articles:
  • Margoliash, D. (1997a) Distributed time-domain representations in the birdsong system. Neuron, 19(5): 963-966.
  • Margoliash, D. (1997b) Functional organization of forebrain pathways for song production and perception. J. Neurobiol., 33(5): 671-693.
    • Speaker: John Hopfield
    Title: How do we think so fast?
    Information Representation, Action Potentials, and Neural Computation
    Related
    articles:
  • Pattern recognition computation using action potential timing for stimulus representation, Nature, 33-36, July 6, 1995.
  • Transforming Neural Computations and Representing Time, PNAS 93, pp 15440-15444, 1996.

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