Postsynaptic calcium, but not cumulative depolarization, is necessary for the induction of associative plasticity in Hermissenda

The neuronal modifications that underlie associative memory in Hermissenda have their origins in a synaptic interaction between the visual and vestibular systems, and can be mimicked by contiguous in vitro stimulation of these converging pathways. At the offset of vestibular stimulation (i.e., hair cell activity), the B photoreceptors are briefly released from synaptic inhibition resulting in a slight depolarization (2–4 mV). If contiguous pairings of light-induced depolarization and presynaptic vestibular activity occur in close temporal succession, this depolarization “accumulates” and has been hypothesized to culminate in a sustained rise in intracellular Ca2+ and a resultant Ca(2+)-mediated phosphorylation of K+ channels as well as an associated increase in input resistance. Here we demonstrate that this cumulative depolarization is neither necessary nor sufficient for the biophysical modifications of the B cell membrane indicative of memory formation. Consistent with several recent reports of one-trial learning in Hermissenda, one pairing of light with mechanical stimulation of the vestibular hair cells resulted in a rise in neuronal input resistance across the B cell membrane that was attenuated by a prepairing iontophoretic injection of the Ca2+ chelator EGTA (25 mM), indicating that this potentiation was Ca2+ dependent. However, the use of a single pairing negates the possibility of an accumulation of depolarization across trials. In a subsequent experiment, B photoreceptors underwent a cumulative depolarization, and a coincident rise in input resistance, during multiple pairings of light and hair cell stimulation. However, if the B photoreceptor was voltage clamped at its initial resting potential before and after each pairing, thus eliminating the cumulative depolarization, the rise in resistance not only persisted, but was enhanced. Moreover, if unpaired light presentations were followed by a current-induced depolarization (to mimic cumulative depolarization), no increase in input resistance was detected. To assess directly the effect of a cumulative depolarization on the voltage-dependent Ca2+ current, an analysis of the inward current on the B cell soma membrane was conducted. It was determined that (1) the inward current may undergo a partial inactivation during sustained depolarization, (2) the peak current was depressed during repetitive depolarizations, and (3) the peak current underwent a steady- state inactivation, such that it was reduced when elicited from holding potentials more positive than -60 mV. The analysis of this current suggests that pairings of light and presynaptic activity would reduce voltage-dependent Ca2+ influx when those pairings are conducted at depolarized membrane potentials, such as during cumulative depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

[1]  T. Crow,et al.  Light paired with serotonin in vivo produces both short- and long-term enhancement of generator potentials of identified B-photoreceptors in Hermissenda , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  D L Alkon,et al.  Light- and voltage-dependent increases of calcium ion concentration in molluscan photoreceptors. , 1984, Journal of neurophysiology.

[3]  N Dale,et al.  Second messengers involved in the two processes of presynaptic facilitation that contribute to sensitization and dishabituation in Aplysia sensory neurons. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[4]  D L Alkon,et al.  Voltage-dependent calcium and calcium-activated potassium currents of a molluscan photoreceptor. , 1984, Biophysical journal.

[5]  M. Fanselow,et al.  Contextual conditioning with massed versus distributed unconditional stimuli in the absence of explicit conditional stimuli. , 1988, Journal of experimental psychology. Animal behavior processes.

[6]  D L Alkon,et al.  Biophysical and behavioral correlates of memory storage, degradation, and reactivation. , 1992, Behavioral neuroscience.

[7]  S. Hagiwara,et al.  The calcium channel , 1983, Trends in Neurosciences.

[8]  Makoto Sato,et al.  A single GTP-binding protein regulates K+-channels coupled with dopamine, histamine and acetylcholine receptors , 1987, Nature.

[9]  J. Farley,et al.  Protein kinase C activation induces conductance changes in Hermissenda photoreceptors like those seen in associative learning , 1986, Nature.

[10]  D L Alkon,et al.  Reduction of two voltage-dependent K+ currents mediates retention of a learned association. , 1985, Behavioral and neural biology.

[11]  D L Alkon,et al.  Regulation of Hermissenda K+ Channels by Cytoplasmic and Membrane‐Associated C‐Kinase , 1988, Journal of neurochemistry.

[12]  J. Farley,et al.  Contingency learning and causal detection in Hermissenda: I. Behavior. , 1987, Behavioral neuroscience.

[13]  Philip Goelet,et al.  Some principles emerging from the study of short- and long-term memory , 1986, Neuroscience Research.

[14]  D. Alkon,et al.  Classical conditioning and protein kinase C activation regulate the same single potassium channel in Hermissenda crassicornis photoreceptors. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Farley,et al.  Protein kinase C activation induces conductance changes in Hermissenda photoreceptors like those seen in associative learning , 1986, Nature.

[16]  T. Carew,et al.  Pharmacological dissociation of modulatory effects of serotonin in Aplysia sensory neurons. , 1991, Science.

[17]  D. A. Baxter,et al.  Neural and Molecular Bases of Nonassociative and Associative Learning in Aplysia a , 1991, Annals of the New York Academy of Sciences.

[18]  D. Alkon,et al.  Cellular mechanisms of learning, memory, and information storage. , 1985, Annual review of psychology.

[19]  R. Eckert,et al.  Calcium‐mediated inactivation of the calcium conductance in caesium‐loaded giant neurones of Aplysia californica. , 1981, The Journal of physiology.

[20]  D. Alkon.  Calcium-mediated reduction of ionic currents: a biophysical memory trace. , 1984, Science.

[21]  T. Crow.  Cellular and molecular analysis of associative learning and memory in Hermissenda , 1988, Trends in Neurosciences.

[22]  D L Alkon,et al.  Sequential modification of membrane currents with classical conditioning. , 1988, Biophysical journal.

[23]  D. Alkon,et al.  GABA-induced potentiation of neuronal excitability occurs during contiguous pairings with intracellular calcium elevation , 1991, Brain Research.

[24]  D L Alkon,et al.  Acquisition of conditioned associations in Hermissenda: additive effects of contiguity and the forward interstimulus interval. , 1990, Behavioral neuroscience.

[25]  D. L. Alkon,et al.  Membrane changes in a single photoreceptor cause associative learning in Hermissenda. , 1983, Science.

[26]  Daniel L. Alkon,et al.  The interstimulus interval and classical conditioning in the marine snail Hermissenda crassicornis , 1989, Behavioural Brain Research.

[27]  R. Tsien,et al.  Multiple types of neuronal calcium channels and their selective modulation , 1988, Trends in Neurosciences.

[28]  D. L. Alkon,et al.  Membrane depolarization accumulates during acquisition of an associative behavioral change. , 1980, Science.

[29]  P. Kaplan.  Importance of relative temporal parameters in trace autoshaping: From excitation to inhibition. , 1984 .

[30]  R. Tsien.  Calcium channels in excitable cell membranes. , 1983, Annual review of physiology.

[31]  D. Johnston,et al.  Induction of long-term potentiation at hippocampal mossy-fiber synapses follows a Hebbian rule. , 1990, Journal of neurophysiology.

[32]  D. Alkon,et al.  Regulation of short-term associative memory by calcium-dependent protein kinase , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  T. Carew,et al.  Invertebrate learning and memory: from behavior to molecules. , 1986, Annual review of neuroscience.

[34]  D. Alkon,et al.  In vitro associative conditioning of Hermissenda: cumulative depolarization of type B photoreceptors and short-term associative behavioral changes. , 1987, Journal of neurophysiology.

[35]  E. Kandel,et al.  A cellular mechanism of classical conditioning in Aplysia: activity-dependent amplification of presynaptic facilitation. , 1983, Science.

[36]  John H. Byrne,et al.  Membrane responses and changes in cAMP levels in Aplysia sensory neurons produced by serotonin, tryptamine, FMRFamide and small cardioactive peptideB (SCPB) , 1985, Neuroscience Letters.