Neuromodulation in invertebrate sensory systems: from biophysics to behavior
1 Department of Physics, Santa Clara University, Santa Clara, CA 95053,
USA
2 Department of Biology, Santa Clara University, Santa Clara, CA 95053,
USA
* Author for correspondence (e-mail: JBirmingham{at}scu.edu)
Accepted 9 July 2003
![]() |
Summary |
---|
Key words: Neuromodulation, invertebrate, gain modulation, sensory
![]() |
Introduction |
---|
A neuromodulatory effect typically begins with the binding of a peptide or
other small molecule to a metabotropic receptor. This triggers a cascade of
biochemical reactions that ultimately changes the physiology of the cell and
can elicit much more complex effects than the simple excitation or inhibition
of classical neurotransmission. These may include modification of a neuron's
membrane resistance, firing rate or bursting properties
(Combes et al., 1997), the
dynamics of adaptation (Zhang et al.,
1992
), the strength of its synaptic outputs, or even the shape of
the action potential itself (Dunlap and
Fischbach, 1978
). Excellent general reviews of neuromodulation can
be found in the literature (Kupfermann,
1979
; Kaczmarek and Levitan,
1987
; Lopez and Brown,
1992
; Katz and Frost,
1996
).
An understanding of the functional significance of neuromodulation may emerge from correlations of the cellular effects of a neuromodulator with the behavioral or physiological changes it induces in an animal. To such an end, research in invertebrate sensory systems is particularly advantageous. Obviously, invertebrate nervous systems are simpler than those of vertebrates. They have fewer cells that are generally larger and easier to maintain in vitro. In many species neurons are readily identifiable, and their synaptic connections have been thoroughly mapped. Individual invertebrate neurons can have significant or even unique roles in determining behavior, and typically only a few layers of neural processing separate sensory input from motor output. Finally, the simplicity inherent in invertebrate systems facilitates detailed mathematical modeling at both the cellular and network level.
One common effect of neuromodulation is to increase sensitivity of receptor
neurons to their particular stimulus. In other words, neuromodulation can
decrease the threshold stimulus required for generating both action potentials
and behavioral responses. For example, in the male silkworm moth
(Antheraea polyphemus) octopamine enhances the sensitivity of neurons
that detect pheromones (Pophof,
2000). This change in receptor sensitivity correlates with the
increased behavioral sensitivity seen in males of several other moth species
after octopamine injection (Linn and
Roelofs, 1986
; Linn et al.,
1992
,
1996
). Male cabbage looper
moths (Trichoplusia ni), for example, detect pheromones at a
concentration two orders of magnitude lower than before injection of the
modulator (Linn and Roelofs,
1986
). Octopamine presumably improves the ability of males to
follow the odor plumes of sex pheromones emitted by females.
Understanding the function of a modulator is not always so easily
interpretable. In addition to identification of the biophysical mechanisms
involved, knowledge of the role neuromodulation plays in network activity may
be required (Mercer, 1999).
Below we discuss several examples of neuromodulation in invertebrate sensory
systems that have been studied on a number of levels, from the effects on ion
channels all the way up to behavior. The role of neuromodulation in several
other well-studied invertebrate sensory systems has previously been reviewed
(Pasztor, 1989
).
![]() |
The classic example of neuromodulation in an invertebrate sensory system |
---|
![]() |
Automodulation of the gain of a primary sensory organ |
---|
|
The tetrapeptide FMRFamide affects the gain of neurons that maintain
osmotic balance in the medicinal leech Hirudo medicinalis
(Wenning and Calabrese, 1995).
Ordinarily, fresh water leeches minimize solute loss by reabsorbing ions from
the urine. However, after a blood meal the concentration of extracellular
chloride can triple (Zerbst-Boroffka et
al., 1997
). Under these conditions salt reabsorption across the
epithelia of urine-forming nephridia decreases, allowing the animal to excrete
the excess solute. The nephridial nerve cells (NNCs) mediate this
physiological change. They monitor extracellular chloride concentration and
secrete FMRFamide to regulate the activity of both the urine-forming cells as
well as the NNCs themselves (Wenning et al.,
1993
,
2001
).
By modulating its own release, FMRFamide adjusts the chloride conductance
and hence the gain of the NNC. Between meals chloride efflux depolarizes the
cells, causing them to fire periodic bursts of action potentials that convey
information about chloride concentration to the central nervous system
(Wenning, 1989). This bursting
also releases both a neurotransmitter and FMRFamide from neurosecretory
terminals innervating the nephridia
(Wenning et al., 1993
). In
addition to its effects on urine formation, the peptide inhibits its own
release and partially inactivates the resting outward chloride conductance,
thereby reducing the NNC chloride receptor gain
(Wenning and Calabrese, 1995
).
In contrast, the high extracellular chloride concentration present after a
blood meal inhibits the same chloride conductance as FMRFamide. As the NNCs
hyperpolarize toward the potassium equilibrium potential, peptide release
stops altogether (Wenning and Calabrese,
1995
). Under these conditions, the chloride conductance depends
solely on the concentration of extracellular chloride. This makes the NNCs
more sensitive to chloride and primes them to monitor the return to normal
extracellular levels of the ion. As the chloride concentration decreases to
the normal steady state levels, chloride channels in the NNCs re-open,
allowing chloride efflux to resume. The resulting membrane depolarization
initiates the normal periodic bursting that releases FMRFamide.
![]() |
Modulation of the interaction between sensory circuits of different modalities |
---|
Sensory information from photoreceptors and mechanoreceptors converges on
type B cells to elicit phototactic behavior. Both GABA and serotonin act
through the same biochemical pathway in these neurons
(Schuman and Clark, 1994;
Schultz and Clark, 1997
).
GABA, released by hair cells, binds to metabotropic receptors on the type B
photoreceptors, stimulating phospholipase A2 to release arachidonic
acid and thereby activate protein kinase C (PKC)
(Muzzio et al., 2001
).
Serotonin also modulates the function of type B photoreceptors via a
PKC-dependent mechanism (Schuman and
Clark, 1994
; Frysztak and
Crow, 1997
). The injection of PKC into B cells and the activation
of endogenous PKC both increase membrane excitability by phosphorylating
potassium channels (Farley and Auerbach,
1986
; Alkon et al.,
1988
). The subsequent reduction in K+ conductance
lengthens action potentials while decreasing the amplitude of the
after-hyperpolarization (Farley and
Auerbach, 1986
; Matzel et al.,
1992
; Gandhi and Matzel,
2000
). In addition, serotonin augments a
hyperpolarization-activated inward current that is active at the resting
potential in these cells (Acosta-Urquidi
and Crow, 1993
). All of these mechanisms prolong the presynaptic
depolarization of B cells, promoting increased transmitter release and
facilitation of postsynaptic inhibition of type A photoreceptors.
![]() |
Multiple neuromodulatory effects on sensory information in a motor control network |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
One of the most common types of feCO neurons generates spike trains with a
tonic component that reflects joint position, as well as a phasic component
that describes movement of the tibia. Application of physiologically relevant
concentrations of octopamine expands the range of tonic firing frequencies
without affecting phasic responses
(Matheson, 1997). This would
suggest that octopamine might strengthen the reflex generated by these cells.
However, octopamine also indirectly increases tonic inhibition at the
sensory-motor terminal due to its enhancement of the firing rates of other
neurons (Matheson, 1997
).
Since it augments both the excitability and the presynaptic inhibition of feCO
neurons, the net effect of octopamine on the reflex is unclear. The
consequence for any particular feCO input to the motor system would depend on
the balance between the two neuromodulatory effects and could be
stimulus-dependent. Determining the physiological importance of octopamine in
this system will require a detailed understanding of the interactions between
particular feCO neurons in the intact neural circuit.
![]() |
Neuromodulation in sensory areas of a central nervous system |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Octopaminergic and serotonergic processes branch throughout the bee's
visual system and brain, suggesting that the amines modulate various functions
of the central nervous system
(Schürmann and Klemm,
1984; Kreissl et al.,
1994
; Bicker, 1999
)
including olfaction and memory (Mercer and
Menzel, 1982
; Bicker and
Menzel, 1989
; Bicker,
1999
). Octopamine and serotonin are released in the CNS under
different circumstances. Octopamine levels appear to increase during food
arousal (Braun and Bicker,
1992
; Bicker,
1999
). This effect of food is supported by the observation that
the injection of octopamine, but not dopamine or serotonin, into the antennal
lobe of the bee (Hildebrandt and
Müller, 1995a
) increases protein kinase A (PKA) levels in the
same manner as sucrose stimulation
(Hildebrandt and Müller,
1995b
). On the other hand, serotonergic modulation of various
insect sensory systems is subject to circadian control. For example, serotonin
application increases photoreceptor sensitivity by modifying potassium channel
kinetics, mimicking the increased sensitivity seen at night
(Cuttle et al., 1995
;
Hevers and Hardie, 1995
.)
Moreover, light suppresses the activity of serotonin-immunoreactive neurons in
the optic lobe of the butterfly Papilla xuthus
(Ichikawa, 1994
), and
serotonin levels in the sphinx moth Manduca sexta peak around dawn
and dusk (Kloppenburg et al.,
1999
). The multiple effects of amines in the bee CNS are probably
mediated by a number of different receptors. The pharmacological properties of
octopamine receptors in the bee's mushroom bodies differ from those in other
parts of the brain (Erber et al.,
1993
), for example. A more complete identification and
understanding of neuromodulatory effects in the sensory CNS will require
continued progress in the application of molecular biological techniques
(Maleszka, 2000
;
Blenau and Baumann, 2001
).
![]() |
Conclusion |
---|
![]() |
Acknowledgments |
---|
![]() |
References |
---|
Acosta-Urquidi, J. and Crow, T. (1993).
Differential modulation of voltage-dependent currents in Hermissenda
type B photoreceptors by serotonin. J. Neurophysiol.
70,541
-548.
Adamo, S. A., Linn, C. E., Jr and Hoy, R. R. (1995). The role of neurohormonal octopamine during `fight or flight' behaviour in the field cricket Gryllus bimaculatus. J. Exp. Biol. 198,1691 -1700.[Medline]
Alkon, D. L., Naito, S., Kubota, M., Chen, C., Bank, B., Smallwood, J., Gallant, P. and Rasmussen, H. (1988). Regulation of Hermissenda K+ channels by cytoplasmic and membrane-associated C-kinase. J. Neurochem. 51,903 -917.[Medline]
Baxter, D. A. and Byrne, J. H. (1989).
Serotonergic modulation of two potassium currents in the pleural sensory
neurons of Aplysia. J. Neurophysiol.
62,665
-679.
Baxter, D. A. and Byrne, J. H. (1990).
Differential effects of cAMP and serotonin on membrane current,
action-potential duration, and excitability in somata of pleural sensory
neurons of Aplysia. J. Neurophysiol.
64,978
-990.
Baxter, D. A., Canavier, C. C., Clark, J. W., Jr, and Byrne, J.
H. (1999). Computational model of the serotonergic modulation
of sensory neurons in Aplysia. J.
Neurophysiol. 82,2914
-2935.
Bicker, G. (1999). Biogenic amines in the brain of the honeybee: cellular distribution, development, and behavioral functions. Microsc. Res. Tech. 44,166 -178.[CrossRef][Medline]
Bicker, G. and Menzel, R. (1989). Chemical codes for the control of behaviour in arthropods. Nature 337,33 -39.[CrossRef][Medline]
Blenau, W. and Baumann, A. (2001). Molecular and pharmacological properties of insect biogenic amine receptors: lessons from Drosophila melanogaster and Apis mellifera. Arch. Insect Biochem. Physiol. 48, 13-38.[CrossRef][Medline]
Braun, G. and Bicker, G. (1992). Habituation of
an appetitive reflex in the honeybee. J. Neurophysiol.
67,588
-598.
Burrows, M. (1987). Parallel processing of proprioceptive signals by spiking local interneurons and motor neurons in the locust. J. Neurosci. 7,1064 -1080.[Abstract]
Burrows, M. and Laurent, G. (1993). Synaptic potentials in the central terminals of locust proprioceptive afferents generated by other afferents from the same sense organ. J. Neurosci. 13,808 -819.[Abstract]
Burrows, M. and Matheson, T. (1994). A presynaptic gain control mechanism among sensory neurons of a locust leg proprioceptor. J. Neurosci. 14,272 -282.[Abstract]
Byrne, J. H. and Kandel, E. R. (1996). Presynaptic facilitation revisited: state and time dependence. J. Neurosci. 16,425 -435.[Abstract]
Claassen, D. E. and Kammer, A. E. (1986). Effects of octopamine, dopamine, and serotonin on production of flight motor output by thoracic ganglia of Manduca sexta. J. Neurobiol. 17,1 -14.[Medline]
Combes, D., Simmers, J. and Moulins, M. (1997). Conditional dendritic oscillators in a lobster mechanoreceptor neurone. J. Physiol. 499,161 -177.[Abstract]
Crow, T. and Tian, L.-M. (2000). Monosynaptic
connections between identified A and B photoreceptors and interneurons in
Hermissenda: evidence for labeled-lines. J.
Neurophysiol. 84,367
-375.
Crow, T. J. and Alkon, D. L. (1978). Retention of an associative behavioral change in Hermissenda. Science 201,1239 -1241.[Medline]
Cuttle, M. F., Hevers, W., Laughlin, S. B. and Hardie, R. C. (1995). Diurnal modulation of photoreceptor potassium conductance in the locust. J. Comp. Physiol. A 176,307 -316.
Davenport, A. P. and Evans, P. D. (1984). Stress-induced changes in the octopamine levels of insect haemolymph. Insect Biochem. 14,135 -143.[CrossRef]
Dunlap, K. and Fischbach, G. D. (1978). Neurotransmitters decrease the calcium component of sensory neurone action potentials. Nature 276,837 -839.[Medline]
Erber, J. (1984). Response changes of single neurons during learning in the honeybee. In Primary Neural Substrates of Learning and Behavioural Change (ed. D. L. Alkon and J. Farley), pp. 275-285. New York: Cambridge University Press.
Erber, J. and Kloppenburg, P. (1995). The modulatory effects of serotonin and octopamine in the visual system of the honeybee (Apis mellifera L.). I. Behavioral analysis of the motion-sensitive antennal reflex. J. Comp. Physiol. A 176,111 -118.
Erber, J., Kloppenburg, P. and Schiedler, A. (1993). Neuromodulation by serotonin and octopamine in the honeybee: behaviour, neuroanatomy and electrophysiology. Experientia 49,1073 -1083.
Erber, J. and Schildberger, K. (1980). Conditioning of an antennal reflex to visual stimuli in bees (Apis mellifera L.). J. Comp. Physiol. 135,217 -225.
Farley, J. and Auerbach, S. (1986). Protein kinase C activation induces conductance changes in Hermissenda photoreceptors like those seen in associative learning. Nature 319,220 -223.[Medline]
Farley, J. and Han, Y. (1997). Ionic basis of
learning-correlated excitability changes in Hermissenda type A
photoreceptors. J. Neurophysiol.
77,1861
-1888.
Fellous, J.-M. and Linster, C. (1998). Computational models of neuromodulation. Neural Computation 10,771 -805.[Abstract]
Field, L. H. and Matheson, T. (1998). Chordotonal organs of insects. Adv. Insect Physiol. 27, 1-228.
Field, L. H. and Rind, F. C. (1981). A single insect chordotonal organ mediates inter- and intra-segmental leg reflexes. Comp. Biochem. Physiol. 68A,99 -102.[CrossRef]
Frysztak, R. J. and Crow, T. (1997). Synaptic
enhancement and enhanced excitability in presynaptic and postsynaptic neurons
in the conditioned stimulus pathway of Hermissenda. J.
Neurosci. 17,4426
-4433.
Gandhi, C. C. and Matzel, L. D. (2000).
Modulation of presynaptic action potential kinetics underlies synaptic
facilitation of type B photoreceptors after associative conditioning in
Hermissenda. J. Neurosci.
20,2022
-2035.
Goh, Y. and Alkon, D. L. (1984). Sensory,
interneuronal, and motor interactions within Hermissenda visual
pathway. J. Neurophysiol.
52,156
-169.
Heran, H. (1959). Wahrnehmung und Regelung der Flugeigengeschwindigkeit bei Apis mellifera L. Z. Vergl. Physiol. 42,103 -163.
Hertel, H. and Maronde, U. (1987). The physiology and morphology of centrally projecting visual interneurones in the honeybee brain. J. Exp. Biol. 133,301 -315.
Hertel, H., Schäfer, S. and Maronde, U. (1987). The physiology and morphology of visual comissures in the honeybee brain. J. Exp. Biol. 133,283 -300.
Hevers, W. and Hardie, R. C. (1995). Serotonin modulates the voltage dependence of delayed rectifier and Shaker potassium channels in Drosophila photoreceptors. Nature 14,845 -856.
Hildebrandt, H. and Müller, U. (1995a). Octopamine mediates rapid stimulation of protein kinase A in the antennal lobe of honeybees. J. Neurobiol. 27, 44-50.[Medline]
Hildebrandt, H. and Müller, U. (1995b). PKA activity in the antennal lobe of honeybees is regulated by chemosensory stimulation in vivo. Brain Res. 679,281 -288.[CrossRef][Medline]
Ichikawa, T. (1994). Light suppresses the activity of serotonin-immunoreactive neurons in the optic lobe of the swallowtail butterfly. Neurosci. Lett. 172,115 -118.[CrossRef][Medline]
Kaczmarek, L. K. and Levitan, I. B. (1987) (ed). Neuromodulation: The Biochemical Control of Neuronal Excitability. New York: Oxford University Press.
Kandel, E. R. (2001). The molecular biology of
memory storage: a dialogue between genes and synapses.
Science 294,1030
-1038.
Katz, P. S. and Frost, W. N. (1996). Intrinsic neuromodulation: altering neuronal circuits from within. Trends Neurosci. 19,54 -61.[CrossRef][Medline]
Klein, M. and Kandel, E. R. (1980). Mechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia. Proc. Natl. Acad. Sci. USA 77,6912 -6916.[Abstract]
Kloppenburg, P. and Erber, J. (1995). The modulatory effects of serotonin and octopamine in the visual system of the honey bee (Apis mellifera L.) II. Electrophysiological analysis of motion-sensitive neurons in the lobula. J. Comp. Physiol. A 176,119 -129.
Kloppenburg, P., Ferns, D. and Mercer, A. R.
(1999). Serotonin enhances central olfactory neuron responses to
female sex pheromone in the male sphinx moth Manduca sexta.
J. Neurosci. 19,8172
-8181.
Kreissl, S., Eichmüller, S., Bicker, G., Rapus, J. and Eckert, M. (1994). Octopamine-like immunoreactivity in the brain and subesophageal ganglion of the honeybee. J. Comp. Neurol. 348,583 -595.[Medline]
Kupfermann, I. (1979). Modulatory actions of neurotransmitters. Annu. Rev. Neurosci. 2, 447-465.[CrossRef][Medline]
Linn, C. E., Jr, Campbell, M. G., Poole, K. R., Wu, W.-Q. and Roelofs, W. L. (1996). Effects of photoperiod on the circadian timing of pheromone response in male Trichoplusia ni: relationship to the modulatory action of octopamine. J. Insect Physiol. 42,881 -891.[CrossRef]
Linn, C. E., Jr, Campbell, M. G. and Roelofs, W. L. (1992). Photoperiod cues and the modulatory action of octopamine and 5-hydroxytryptamine on locomotor and pheromone response in male gypsy moths, Lymantria dispar. Arch. Insect Biochem. Physiol. 20,265 -284.
Linn, C. E., Jr and Roelofs, W. L. (1986). Modulatory effects of octopamine and serotonin on male sensitivity and periodicity of response to sex pheromone in the cabbage looper moth, Trichoplusia ni. Arch. Insect Biochem. Physiol. 3,161 -172.
Liu, Q.-R., Hattar, S., Endo, S., MacPhee, K., Zhang, H.,
Cleary, L. J., Byrne, J. H. and Eskin, A. (1997). A
developmental gene (Tolloid/BMP-1) is regulated in Aplysia
neurons by treatments that induce long-term sensitization. J.
Neurosci. 17,755
-764.
Livingstone, M. S., Harris-Warrick, R. M. and Kravitz, E. A. (1980). Serotonin and octopamine produce opposite postures in lobsters. Science 208,76 -79.
Lopez, H. S. and Brown, A. M. (1992). Neuromodulation. Curr. Opin. Neurobiol. 2, 317-322.[Medline]
Maleszka, R. (2000). Molecules to behaviour in the honeybee - the emergence of comparative neurogenomics. Trends Neurosci. 23,513 -514.[CrossRef]
Marinesco, S. and Carew, T. J. (2002).
Serotonin release evoked by tail nerve stimulation in the CNS of
Aplysia: characterization and relationship to heterosynaptic
plasticity. J. Neurosci.
22,2299
-2312.
Matheson, T. (1990). Responses and locations of neurones in the locust metathoracic femoral chordotonal organ. J. Comp. Physiol. A 166,915 -927.
Matheson, T. (1997). Octopamine modulates the
responses and presynaptic inhibition of proprioceptive sensory neurones in the
locust Schistocerca gregaria. J. Exp. Biol.
200,1317
-1325.
Matzel, L. D., Collin, C. and Alkon, D. L. (1992). Biophysical and behavioral correlates of memory storage, degradation, and reactivation. Behav. Neurosci. 106,954 -963.[CrossRef][Medline]
Mercer, A. R. (1999). Changing the way we perceive things: sensory systems modulation. In Beyond Neurotransmission: Neuromodulation and its Importance for Information Processing (ed. P. S. Katz), pp.198 -240. New York: Oxford University Press.
Mercer, A. R. and Menzel, R. (1982). The effects of biogenic amines on conditioned and unconditioned responses to olfactory stimuli in the honeybee Apis mellifera. J. Comp. Physiol. 145,363 -368.
Müller, U. and Carew, T. J. (1998). Serotonin induces temporally and mechanistically distinct phases of persistent PKA activity in Aplysia sensory neurons. Neuron 21,1423 -1434.[Medline]
Muzzio, I. A., Gandhi, C. C., Manyam, U., Pesnell, A. and
Matzel, L. D. (2001). Receptor-stimulated phospholipase
A2 liberates arachidonic acid and regulates neuronal excitability
through protein kinase C. J. Neurophysiol.
85,1639
-1647.
Orchard, I., Loughton, B. G. and Webb, R. A. (1981). Octopamine and short-term hyperlipaemia in the locust. Gen. Comp. Endocrinol. 45,175 -180.[Medline]
Pasztor, V. M. (1989). Modulation of sensitivity in invertebrate sensory receptors. Semin. Neurosci. 1,5 -14.
Pophof, B. (2000). Octopamine modulates the sensitivity of silkmoth pheromone receptor neurons. J. Comp. Physiol. A 186,307 -313.[Medline]
Roeder, T. (1999). Octopamine in invertebrates. Prog. Neurobiol. 59,533 -561.[CrossRef][Medline]
Schultz, L. M. and Clark, G. A. (1997). GABA-induced synaptic facilitation at type B to A photoreceptor connections in Hermissenda. Brain. Res. Bull. 42,377 -383.[CrossRef][Medline]
Schuman, E. M. and Clark, G. A. (1994). Synaptic facilitation at connections of Hermissenda type B photoreceptors. J. Neurosci. 14,1613 -1622.[Abstract]
Schürmann, F. W. and Klemm, N. (1984). Serotonin-immunoreactive neurons in the brain of the honeybee. J. Comp. Neurol. 225,570 -580.[Medline]
Usherwood, P. N. R., Runion, H. I. and Campbell, J. I. (1968). Structure and physiology of a chordotonal organ in the locust leg. J. Exp. Biol. 48,305 -323.
Walsh, J. P. and Byrne, J. H. (1989).
Modulation of a steady-state Ca2+-activated, K+ current
in tail sensory neurons of Aplysia: role of serotonin and cAMP.
J. Neurophysiol. 61,32
-44.
Wenning, A. (1989). Properties of a set of internal receptors in the medicinal leech: the nephridial nerve cells monitor extracellular chloride concentration. J. Exp. Biol. 143,115 -132.
Wenning, A., Cahill, M. A., Hoeger, U. and Calabrese, R. L.
(1993). Sensory and neurosecretory innervation of leech nephridia
is accomplished by a single neurone containing FMRFamide. J. Exp.
Biol. 182,81
-96.
Wenning, A. and Calabrese, R. L. (1995). An endogenous peptide modulates the activity of a sensory neurone in the leech Hirudo medicinalis. J. Exp. Biol. 198,1405 -1415.[Medline]
Wenning, A., Erxleben, C. F. J. and Calabrese, R. L.
(2001). Indirectly gated Cl--dependent Cl-
channels sense physiological changes of extracellular chloride in the leech.
J. Neurophysiol. 86,1826
-1838.
Zerbst-Boroffka, I., Bazin, B. and Wenning, A.
(1997). Chloride secretion drives urine formation in leech
nephridia. J. Exp. Biol.
200,2217
-2227.
Zhang, B. G., Torkkeli, P. H. and French, A. S. (1992). Octopamine selectively modifies the slow component of sensory adaptation in an insect mechanoreceptor. Brain. Res. 591,351 -355.[CrossRef][Medline]
Zhang, F., Endo, S., Cleary, L. J., Eskin, A. and Byrne, J.
H. (1997). Role of transforming growth factor-ß in
long-term synaptic facilitation in Aplysia.
Science 275,1318
-1320.