The formation, maintenance and remodeling of synapses involves regulated expression and targeting of specific transmitter receptors to sites of cellular contact. Presynaptic input and input-derived signals are potentially important regulators of receptor expression at neuron–neuron synapses. In particular, expression of specific subtypes of neuronal ionotropic glutamate and acetylcholine receptors are controlled by synaptic activity and/or neuregulin-type growth factors1,2. When chick sympathetic neurons establish contact with their preand postsynaptic partners during embryonic development, the magnitude of inward current responses to acetylcholine (ACh) increases, the number, localization and biophysical profile of nAChR channels are altered, and mRNA levels for the predominant nAChR subunits (a3, a5, a7, b4) are upregulated3,4. Despite the general enhancement of nicotinic responses evident with ganglionic development in vivo, sympathetic neurons are heterogeneous in the levels and subtypes of nAChRs expressed3,4. Differences in receptor expression may be due to distinct, target-derived influences5,6, as neurons within individual ganglia innervate a variety of peripheral targets. In-vivo studies reveal aberrant receptor expression by autonomic neurons deprived of target contact7,8. Innervation of sympathetic neurons in vitro in the absence of target tissues reproduces only a subset of the changes that are observed with development in vivo9–11. The current study demonstrates retrograde, target-specific regulation of the levels and functional profile of receptors expressed at antecedent interneuronal synapses.