Aplysia R15 neuron

From Scholarpedia
Fred H. Sieling and Robert Butera (2011), Scholarpedia, 6(10):4181. doi:10.4249/scholarpedia.4181 revision #126753 [link to/cite this article]
Jump to: navigation, search
Post-publication activity

Curator: Robert Butera

Figure 2: Location of R15 in the abdominal ganglion. Color added by authors. Adapted from http://www.rsmas.miami.edu/assets/images/aplysia/abdominal-2-large.jpg.
Figure 3: 50 sec of typical bursting activity from R15. Reproduced with permission from Levitan and Levitan (1988).

Neuron R15, located in the abdominal ganglion of the gastropod mollusc Aplysia Californica, is the first intrinsically bursting neuron to receive extensive study using single cell electrophysiology techniques. Much of the investigation of the nature of electrical bursting of single neurons was motivated by the initial study of this neuron, and it was later one of the first to receive extensive study of the role of neuromodulation in biasing single neuron burst dynamics.

Arvanitaki (1941) had recorded electrical activity extracellularly from various neuronal somata that were distinct and visually identifiable. Soon thereafter, the technique of intracellular recording had been invented and was adopted as a tool for investigating the electrical dynamics of visually identifiable neurons in Aplysia. Arvanitaki and Chalazonitis (1955) and simultaneously Tauc (1954) published the first reports of a distinct visually identifiable neuron in the abdominal ganglion of Aplysia, now called R15 (Cogeshall et al., 1966; Frazier et al., 1967).

The study of R15 was accelerated when Eric Kandel adopted Aplysia as his animal model for studying the cellular basis of behavior. Kandel and his colleagues named many of the visually identifiable neurons in the ganglia of Aplysia and mapped out many of Aplysia's neuron circuits. Much of this work continues today.


Electrophysiological Properties of Bursting

Early studies of R15 could find no evidence of rhythmic synaptic input or synchronous activity in connected neurons, leading to the conclusion that bursting in R15 was endogenous. It was shown that isolated somata could continue to burst after ligature (Alving, 1968) or isolated dissection (Chen et al., 1971). The bursting rhythm could also be phase-shifted by well-timed inputs to the soma (Pinsker, 1977), further supporting the idea that the rhythm was intrinsic to the neuron itself. R15 has been referred to as a parabolic burster (Strumwasser, 1968) due to parabolic rise and fall of the interspike interval over the time-course of the burst.

Figure 4: Parabolic bursting of R15. Unpublished data from RJB.

The mechanism of bursting in neuron R15 received extensive study in the 1970s and 1980s. These works are reviewed quite comprehensively in “The generation and modulation of endogenous rhythmicity in the Aplysia bursting pacemaker neurone R15” (Adams and Benson, 1985). In fact, very little experimental work on the ionic basis of bursting in R15 has been published since their comprehensive review article. Early investigators quickly identified several key features associated with the bursting rhythm, features that have now become recognized as common to many intrinsically bursting neurons. These features include:

  • the existence and importance of a "negative slope region" in the current-voltage (I-V) curve;
  • the recognition that the onset, offset, and progression of the burst were associated with ionic conductances that changed slowly during the burst; and
  • the role of an inward cationic current in initiating the burst.

Nevertheless, the literature on this topic is a “chaos of conflicting observations and interpretations” (Adams and Benson, 1985). Some investigators found that a subthreshold oscillation persisted in the presence of tetrodotoxin (TTX), while others did not. Some investigators criticized many of the published studies, as they involved significant changes in the concentrations of Na+ or Ca2+ which significantly altered membrane properties. One laboratory reported that "freshly opened" TTX blocked the subthreshold oscillations, but not if the vial of TTX had been opened for one day. What is agreed upon is that a cationic current is responsible for the negative slope region and the initiation of the burst.

A key point of dispute is the identification of an ionic mechanism that changes slowly during the burst and can account for the termination of the burst. Ideally, this would involve the progressive inactivation of the negative-slope-region (NSR) current responsible for the initiation of the burst or the slow activation of an outward current to counteract this current. Proposed mechanisms have included the slow activation and subsequent inactivation of an outward K+ current (Junge and Stephens, 1973), voltage-activation and Ca2+-inactivation of the NSR current (Adams and Levitan, 1985; Kramer and Zucker, 1985), and a hyperpolarization activated current that summates throughout the burst (Adams, 1985).

While many models of bursting in R15 exist largely based on Adams and Benson's proposed model, exactly how the neuron bursts has never been conclusively resolved. Research on R15's ionic mechanisms largely stopped in the late 1980s. Furthermore, subthreshold currents are difficult to quantify due to their low amplitude compared to other ionic currents in the cell membrane.

Neuromodulation of Bursting

Substances that have been shown to affect the activity of R15 include acetylcholine (Ach), dopamine (DA), Aplysia egg-laying hormone (ELH), Phe-Met-Arg-Phe-amide (FM-RFamide), \(\gamma\)-aminobutyric acid (GABA), serotonin (5-HT), cyclic-adenosine monophosphate (cAMP), and cyclic-guanosine monophosphate (cGMP) (Carpenter et al., 1978; Drummond et al., 1980; Kramer et al., 1988a; Levitan et al., 1987; Levitan and Norman, 1980). Neuromodulators such as DA, 5-HT, ELH, and FM-RFamide have received the most attention, especially 5-HT and DA. DA can bias the cell into a hyperpolarized silent state (Gospe and Wilson, 1980). 5-HT has a more complex effect. At low concentrations, it silences bursting, while at high concentrations it causes elongated bursting and then tonic spiking. These effects occur by activating an inwardly rectifying K+ current at low 5-HT concentrations (Drummond et al., 1980; Benson and Levitan, 1983) and an inward cationic current at higher concentrations of 5-HT (Levitan and Levitan, 1988). 5-HT and DA have generally opposing effects on burst excitability (Lotshaw and Levitan, 1988). Cyclic AMP is the second messenger mediating 5-HT's effects (Lotshaw et al., 1986; Levitan and Levitan, 1988). In addition, there exist dynamic interactions between Ca2+ and cAMP (Kramer et al., 1988). Many of these modulatory effects are mediated intracellularly by cAMP and cGMP.

Figure 5: Low doses of 5-HT hyperpolarize the interburst (and sometimes silence the cell). High doses depolarize and enhance the burst itself and often lead to a transition to spiking. Reproduced with permission from Levitan and Levitan (1988).
Figure 6: 5-HT "turns on" non-brief responses to brief inputs. Reproduced with permission from Levitan and Levitan (1988).
Figure 7: Effects of Serotonin on the IV curve. Reproduced with permission from Butera et al. (1995).

Computational Models of R15 Burst Dynamics and Modulation

Since the mid 70s, several models of R15 have surfaced with varying levels of quantitative and qualitative accuracy. Most models consist of an array of Hodgkin-Huxley (H-H) type ion channels fit to voltage clamp data derived from preparations of the isolated abdominal ganglion bathed in standard ASW or exotic pharmaceutical cocktails. Voltage time-series and steady state current-voltage (I-V) curves obtained under the above conditions were fit and analyzed.

There are several trends in this modeling work. Newer models increasingly stress the relevance of model components to electrophysiological data. As the sophistication of electrophysiology and molecular biology techniques improved, models were able to incorporate more biophysical measurements. From the 70s to the mid-90s, interest peaked in the mechanism of both R15 burst dynamics (Bertram, 1993; Canavier et al. 1991) and mechanisms of neuromodulation by DA and 5-HT (Bertram, 1993; Butera et al., 1995). In all models, there has been an emphasis on applying non-linear systems theory to neurons, e.g., 2-dimensional nullcline analysis in the phase plane (Butera et al., 1997), bifurcation analysis (Butera et al., 1996), and slow-fast timescale decomposition (Rinzel and Lee, 1985; Bertram, 1994; Butera et al., 1996). Rinzel and Lee (1985) showed that using bifurcation analysis, they were able to identify the parameter space where parabolic bursting occurred in their model. These techniques are part of today’s growing literature in dynamical systems theory (Izhikevich 2007). Other interesting avenues opened via R15 models include geometrical analysis of phase response curves (Demir et al. 1997) and the idea of multistability as an information storage mechanism (Canavier et al. 1993, Canavier et al. 1994, Butera 1998, Newman and Butera 2010; see also Multi-stability in neuronal models).

Figure 8: Schematic reproduced with permission from Butera et al. (1995).
Figure 9: Schematic of model from Yu et al. 2004 (Baxter, personal communication).
Figure 10: Evolution of the phase portrait as a parameter is adjusted, showing multiple coexisting stable orbits. (Canavier, personal communication)
R15 models
Reference Salient Contribution
Plant model (Plant 1976) Early biophysical R15 model reproduced many behaviors including parabolic bursting; first H-H type model
Rinzel and Lee 1985 Slow-fast decomposition and bifurcation analysis
Adams and Benson 1985 Synthesis of confusing array of empirical data
Canavier et al. 1990 Demonstrated a period doubling route to chaos in the parametric transition between bursting and spiking
Canavier et al. 1991 Added intracellular Ca2+ balance
Bertram 1993, 1994 Incorporated detailed effects of 5-HT
Canavier et al. 1993, 1994 Showed multistability, 7 modes of activity at one set of parameters
Butera et al. 1995 Incorporated intracellular cAMP and PK pathways; explained effects of DA and 5-HT
Yu et al. 2004 Added Ca2+-calmodulin interactions with cAMP pathway; made dynamical argument for cAMP oscillations

Physiological Function of R15

In the first 30 years of work on R15, little attention was paid to its physiological function; however, in a set of 3 companion papers and two other papers Alevizos et al. (1991abcde) produced convincing and surprising data showing that (1) R15 is likely involved in the minutes-long process of egg laying and (2) although in vitro R15 was the best studied bursting neuron through the 1980s, in vivo it actually does not burst most of the time (1991a). It is hypothesized that R15 bursts during egg laying, but a bout of egg laying was never recorded in vivo. Due to the limitations of the reel-to-reel technology used for electrophysiological recordings at the time, Alevizos et al. were restricted to three hours of intermittent recordings per day. Using modern digital technology and by recording in vivo for 24 hours per day, it is possible that this could be determined conclusively through 24 hour/day continuous monitoring.

Figure 11: Setup of in vivo recordings. Reproduced with permission from Alevizos et al. (1991a).
Figure 12: Possible role of bursting neuron R15 of Aplysia in the control of egg laying behavior. Reproduced from Alevisos (1991d).
Figure 13: Comparison of bursting neurons. Figure 1 from Alevizos et al. (1991e). Biol. Bull. 180(2): 269-275. Reprinted with permission from the Marine Biological Laboratory, Woods Hole, MA.

Relevance to the Modern Study of Bursting Neurons

  • R15 was arguably the best studied bursting neuron of the 1970s and 1980s. However, research waned due to its apparent lack of participation in any well-studied motor central pattern generating circuit. The bursting neurons of the stomatogastric ganglion (STG) are arguably the best studied since the 1990s, and participate in central pattern-generating circuits.
  • Dynamical neuroscience mechanisms. In the study of bursting neurons, the ubiquitous negative slope region (NSR), which is usually thought of as dependent on activation of inward cationic currents, is equally dependent on de- or in-activation of outward K+ current (Butera 1995). This effect is well understood (Izhikevich, 2007), but R15 is the first and best known example.
  • Many examples exist today of well-studied bursting neurons (and other cell types) whose study was heavily informed by these earlier works on R15.
    • Dopamine neurons (Amini et al., 1999)
    • preBötzinger Complex (Butera et al., 1999; Del Negro et al., 2001; Toporikova and Butera, 2010; Dunmyre et al., 2010)
    • Thalamo-cortical relay cells (Huguenard and McCormick, 1992; Wang et al., 1991, 1995)
    • pancreatic \(\beta\) cells (Sherman, 1996; Bertram et al., 2000)
    • neurons of the stomatogastric ganglion (Guckenheimer et al. 1993; Liu et al., 1998; Soto-Trevino et al., 2005)

Open questions

Even given the above mountain of research, the mechanism of bursting in R15 is arguably still unresolved, e.g., is the current responsible for bursting ICa, IK, ICaN, or the mysterious INSR? Since the last experimental analysis of R15 bursting mechanisms in the mid-80s, new molecular and genetic tools have emerged that could put this question to rest. The Aplysia Genome Project may reveal the genetic identities of ion channels that sum or combine to form previously described currents. Digital electrophysiology recording technology allows for full 24-hour recordings of R15 in vivo, which could unambiguously discern its putative role in egg-laying. In short, modern tools and technologies and ability for large scale and long term observability could re-empower all of the questions posed above to be revisited with more conclusive results.

See also

Aplysia, Bursting, Routes into bursting, Neuromodulation, Plant model, Phase response curve, Multi-stability in neuronal models, Aplysia operant conditioning, Stomatogastric ganglion


  • Adams, D. J. and Gage, P. W. (1976). "Gating currents associated with sodium and calcium currents in an aplysia neuron." Science 192(4241): 783-784.
  • Adams, W. B. (1985). "Slow depolarizing and hyperpolarizing currents which mediate bursting in aplysia neurone r15." J Physiol 360: 51-68.
  • Adams, W. B. and Benson, J. A. (1985). "The generation and modulation of endogenous rhythmicity in the aplysia bursting pacemaker neurone R15." Prog Biophys Mol Biol 46(1): 1-49.
  • Adams, W. B. and Levitan I.B. (1985). "Voltage and ion dependences of the slow currents which mediate bursting in Aplysia neurone R15". J Physiol 360: 69-93.
  • Alevizos, A., Weiss, K. R. and Koester, J. (1991a). "Synaptic actions of identified peptidergic neuron r15 in aplysia. I. Activation of respiratory pumping." J Neurosci 11(5): 1263-1274.
  • Alevizos, A., Weiss, K. R. and Koester, J. (1991b). "Synaptic actions of identified peptidergic neuron r15 in aplysia. Ii. Contraction of pleuroabdominal connectives mediated by motoneuron l7." J Neurosci 11(5): 1275-1281.
  • Alevizos, A., Weiss, K. R. and Koester, J. (1991c). "Synaptic actions of identified peptidergic neuron r15 in aplysia. Iii. Activation of the large hermaphroditic duct." J Neurosci 11(5): 1282-1290.
  • Alevizos, A., Skelton, M., Karagogeos, D., Weiss, K. R. and Koester, J. (1991d). "Possible role of bursting neuron r15 of aplysia in the control of egg-laying behavior." Molluscan neurobiology: 61-66.
  • Alevizos, A., Skelton, M., Weiss, K. R. and Koester, J. (1991e). "A comparison of bursting neurons in aplysia." Biol Bull 180(2): 269-275.
  • Alving, B. O. (1968). "Spontaneous activity in isolated somata of aplysia pacemaker neurons." J Gen Physiol 51(1): 29-45.
  • Amini, B., Clark, J. W. and Canavier, C. C. (1999). "Calcium dynamics underlying pacemaker-like and burst firing oscillations in midbrain dopaminergic neurons: A computational study." Journal of Neurophysiology 82(5): 2249-2261.
  • Arvanitaki, A. and Cardot, H. (1941). "Réponses rhytmiques ganglionnaires, graduées en fonction de la polarisation appliquée. Lois des latences et des fréquences." C. R. Soc. Biol. (Paris) 135(1211-1216).
  • Arvanitaki, A. and Chalazonitis, N. (1955). "Les potentiels bioélectriques endocytaires du neurone géant d'aplysia en activité autorhytmique." C. R. Acad. Sci. (Paris) 240: 349-351.
  • Benson J. A. and Levitan I. B. (1983). "Serotonin increases an anomalously rectifying K+ current in the Aplysia neuron R15." Proc Natl Acad Sci USA (80): 3522-3525.
  • Bertram, R. (1993). "A computational study of the effects of serotonin on a molluscan burster neuron." Biol Cybern 69:257-267.
  • Bertram, R. (1994). "Reduced-system analysis of the effects of serotonin on a molluscan burster neuron." Biol Cybern 70(4): 359-368.
  • Bertram, R., Previte, J., Sherman, A., Kinard, T. A. and Satin, L. S. (2000). "The phantom burster model for pancreatic beta-cells." Biophysical Journal 79(6): 2880-2892.
  • Butera, R. J., Rinzel, J. and Smith, J. C. (1999). "Models of respiratory rhythm generation in the pre-bötzinger complex. I. Bursting pacemaker neurons." Journal of Neurophysiology 82(1): 382-397.
  • Butera, R. J. (1998). "Multirhythmic bursting." Chaos 8(1): 274-284.
  • Butera, R. J., Jr., Clark, J. W., Jr., Canavier, C. C., Baxter, D. A. and Byrne, J. H. (1995). "Analysis of the effects of modulatory agents on a modeled bursting neuron: Dynamic interactions between voltage and calcium dependent systems." J Comput Neurosci 2(1): 19-44.
  • Canavier, C. C., Baxter, D. A., Clark, J. W. and Byrne, J. H. (1993). "Nonlinear dynamics in a model neuron provide a novel mechanism for transient synaptic inputs to produce long-term alterations of postsynaptic activity." J Neurophysiol 69(6): 2252-2257.
  • Canavier, C. C., Baxter, D. A., Clark, J. W. and Byrne, J. H. (1994). "Multiple modes of activity in a model neuron suggest a novel mechanism for the effects of neuromodulators." J Neurophysiol 72(2): 872-882.
  • Canavier, C. C., Clark, J. W. and Byrne, J. H. (1991). "Routes to chaos in a model of a bursting neuron." Biophys J. 57(6) 1245-1251.
  • Canavier, C. C., Clark, J. W. and Byrne, J. H. (1991). "Simulation of the bursting activity of neuron r15 in aplysia: Role of ionic currents, calcium balance, and modulatory transmitters." J Neurophysiol 66(6): 2107-2124.
  • Carpenter, D. O., McCreery, M. J., Woodbury, C. M. and Yarowsky, P. J. (1978). Modulation of endogenous discharge in neuron r15 through specific receptors for several neurotransmitters. Abnormal neuronal discharges. N. Chalazonitis and M. Boisson, Raven Press: 189-203.
  • Chen, C. F., Von Baumgarten, R. and Takeda, R. (1971). "Pacemaker properties of completely isolated neurones in aplysia californica." Nat New Biol 233(35): 27-29.
  • Coggeshall, R. E., Kandel, E. R., Kupfermann, I. and Waziri, R. (1966). "A morphological and functional study of a cluster of neurosecretory cells in the abdominal ganglion of aplysia californica." Journal of Cellular Biology 31.
  • Del Negro, C. A., Johnson, S. M., Butera, R. J. and Smith, J. C. (2001). "Models of respiratory rhythm generation in the pre-botzinger complex. Iii. Experimental tests of model predictions." Journal of Neurophysiology 86(1): 59-74.
  • Demir, S. S., Butera, R. J., Jr., DeFranceschi, A. A., Clark, J. W., Jr. and Byrne, J. H. (1997). "Phase sensitivity and entrainment in a modeled bursting neuron." Biophys J 72(2 Pt 1): 579-594.
  • Drummond, A. H., Benson, J. A., and Levitan, I. B. (1980). "Serotonin-induced hyperpolarization of an identified Aplysia neuron is mediated by cyclic amp." Proc Natl Acad Sci U S A 77: 5013-5017.
  • Dunmyre, J. R., Del Negro, C. A. and Rubin, J. E. (2011). "Interactions of persistent sodium and calcium-activated nonspecific cationic currents yield dynamically distinct bursting regimes in a model of respiratory neurons." J Comput Neurosci.
  • Frazier, W. T., Kandel, E. R., Kupfermann, I., Waziri, R. and Coggeshall, R. E. (1967). "Morphological and functional properties of identified neurons in the abdominal ganglion of aplysia californica." Journal of Neurophysiology 30:1288-1351.
  • Gospe, S. M. and Wilson, W. A. (1980). "Dopamine inhibits burst-firing of neurosecretory cell r15 in aplysia californica: Establishment nof a dose-response relationship." Journal of Pharmacology and Experimental Therapeutics 214: 112-118.
  • Guckenheimer, J., Gueron, S. and Harris-Warrick, R. M. (1993). "Mapping the dynamics of a bursting neuron." Philos Trans R Soc Lond B Biol Sci 341(1298): 345-359.
  • Huguenard, J. R. and McCormick, D. A. (1992). "Simulation of the currents involved in rhythmic oscillations in thalamic relay neurons." J Neurophysiol 68(4): 1373-1383.
  • Izhikevich, E. M. (2007). Dynamical systems in neuroscience: The geometry of excitability and bursting. Boston, MIT Press.
  • Junge, D. and Stephens, C. L. (1973). "Cyclic variation of potassium conductance in a burst-generating neurone in Aplysia." J Physiol Lond 235, 155-181.
  • Kandel, E. R. (1979). Behavioral Biology of Aplysia. San Francisco, WH Freeman.
  • Kandel, E. R. Frazier, W. T., Waziri, R. and Coggeshall, R. E. (1967). Direct and common connections among identified neurons in Aplysia. J. Neurophysiology 30:1352–76.
  • Kramer, R. H., Levitan, E. S., Carrow, G. M. and Levitan, I. B. (1988). "Modulation of a subthreshold calcium current by the neuropeptide FMRFamide in aplysia neuron R15." Journal of Neurophysiology 60.
  • Kramer, R. H. and Zucker, R. S. (1985). "Calcium-dependent inward current in Aplysia bursting pace-maker neurones." The Journal of Physiology 362(1): 107-130.
  • Levitan, E. S., Kramer, R. H. and Levitan, I. B. (1987). "Augmentation of bursting pacemaker activity by egg-laying hormone in aplysia neuron r15 is mediated by a cyclic-amp-dependent increase in ca++ and k+ currents." Proc Natl Acad Sci U S A 84: 6307-6311.
  • Levitan E. S, and Levitan I. B. (1988). "Serotonin acting via cyclic AMP enhances both the hyperpolarizing and depolarizing phases of bursting pacemaker activity in the Aplysia neuron R15." J Neurosci 8:1152-1161.
  • Levitan, I. B. and Norman, J. (1980). "Different effects of camp and cgmp derivatives on the activity of an identified neuron: Biochemical and electrophysiological analysis." Brain Res 187: 415-429.
  • Liu, Z., Golowasch, J., Marder, E. and Abbott, L. F. (1998). "A model neuron with activity-dependent conductances regulated by multiple calcium sensors." J Neurosci 18(7): 2309-2320.
  • Lotshaw D. P., Levitan E. S., Levitan I.B. (1986). "Fine tuning of neuronal electrical activity: modulation of several ion channels by intracellular messengers in a single identified nerve cell." J Exp Biol 124: 307-322.
  • Lotshaw D. P. and Levitan I. B. (1988). "Reciprocal modulation of calcium current by serotonin and dopamine in the identified Aplysia neuron R15." Brain Research 439(1-2): 64-76.
  • Newman, J. P. and Butera, R. J. (2010). "Mechanism, dynamics, and biological existence of multistability in a large class of bursting neurons." Chaos 20(2): 023118.
  • Pinsker, H. M. (1977). "Aplysia bursting neurons as endogenous oscillators. I. Phase-response curves for pulsed inhibitory synaptic input." J Neurophysiol 40(3): 527-543.
  • Plant, R. E. and Kim, M. (1976). "Mathematical description of a bursting pacemaker neuron by a modification of the Hodgkin-Huxley equations." Biophys J 16: 227-244.
  • Rinzel, J. and Lee, Y. S. (1987). "Dissection of a model for neuronal parabolic bursting." Journal of Mathematical Biology 25(6): 653-675.
  • Sherman, A. (1996). "Contributions of modeling to understanding stimulus-secretion coupling in pancreatic beta-cells." American Journal of Physiology-Endocrinology and Metabolism 271(2): E362-E372.
  • Soto-Trevino, C., Rabbah, P., Marder, E. and Nadim, F. (2005). "Computational model of electrically coupled, intrinsically distinct pacemaker neurons." J Neurophysiol 94(1): 590-604.
  • Strumwasser, F. (1968). Membrane and intracellular mechanisms governing endogenous activity in neurons. Physiological and biochemical aspects of nervous integration. F. D. Carlson. New Jersey, Prentice-Hall: 329.
  • Tauc, L. (1954). "Réponse de la cellule nerveuse du ganglion abdominal d’aplysia depilans á la stimulation directe intracellulaire." C. R. Acad. Sci. Belles-lett. Arts Clermont-Ferrand 239.
  • Toporikova, N. and Butera, R. (2010). "Two types of independent bursting mechanisms in inspiratory neurons: An integrative model." Journal of Computational Neuroscience: 1-14.
  • Wang, X. J., Golomb, D. and Rinzel, J. (1995). "Emergent spindle oscillations and intermittent burst firing in a thalamic model: Specific neuronal mechanisms." Proc Natl Acad Sci U S A 92(12): 5577-5581.
  • Wang, X. J., Rinzel, J. and Rogawski, M. A. (1991). "A model of the t-type calcium current and the low-threshold spike in thalamic neurons." J Neurophysiol 66(3): 839-850.
  • Yu, X., Byrne, J. H. and Baxter, D. A. (2004). "Modeling interactions between electrical activity and second-messenger cascades in aplysia neuron R15." J Neurophysiol 91(5): 2297-2311.,,
Personal tools

Focal areas