Journal of Neuroscience, Vol 13, 2126-2135, Copyright © 1993 by Society for Neuroscience
Functional uncoupling of inhibitory interneurons plays an important role in short-term sensitization of Aplysia gill and siphon withdrawal reflex
LE Trudeau and VF Castellucci
Laboratoire de Neurobiologie et Comportement, Institut de recherches cliniques de Montreal, Quebec, Canada.
Attempts to explain learning-associated potentiation of synaptic
transmission in model systems such as withdrawal reflexes in the mollusk
Aplysia or the hippocampus of vertebrates have focused on the mechanisms by
which transmitter release is increased in the principal elements of the
circuit. Increased transmission in neuronal networks such as the gill and
siphon withdrawal reflex (GSWR) of Aplysia may, however, also be caused by
a decrease of transmitter release by inhibitory interneurons. The
importance and function of cholinergic inhibitory transmission in the GSWR
network were investigated. Central application of the nicotinic cholinergic
antagonist d-tubocurarine (d- TC) considerably potentiated gill
contractions, evoked either by nerve stimulation or by tactile stimulation
of the siphon. Compound EPSPs evoked in motoneurons upon siphon nerve
stimulation were also significantly prolonged following application of
d-TC, but were unaffected by hexamethonium, a blocker of excitatory ACh
receptors in Aplysia. Recordings from excitatory interneurons showed that
they received excitation followed by powerful inhibitory input upon
stimulation of the siphon nerve. Application of d-TC completely blocked
this rapid inhibition, thus prolonging the compound EPSPs evoked in the
interneurons. These effects were obtained at a concentration of d-TC (100
microM) that almost totally blocked fast inhibitory cholinergic
transmission, but was without effect on monosynaptic connections between
sensory neurons and motoneurons of the reflex. Facilitation of (1) compound
EPSCs in motoneurons and (2) evoked excitatory interneuronal firing was
reduced in preparations already disinhibited by pretreatment with d-TC.
Facilitation of sensory-motor synapses, however, was not reduced in the
presence of d-TC, indicating that facilitatory interneurons are still
activated under cholinergic blockade. These data show that transmission
through the GSWR neuronal network is gated by a feedback inhibitory
mechanism. They also suggest that a reduction of cholinergic inhibition
onto excitatory interneurons may be a mechanism through which transmission
within the GSWR network is increased during various forms of learning, such
as sensitization. These data place new emphasis on the important role of
inhibitory interneurons in determining the plastic properties of neuronal
networks, in both invertebrates and vertebrates.
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