Electrophysiological and immunohistochemical investigation of homeostatic mechanisms to compensate differences in the architecture of neural networks
Final Report Abstract
The goal of my research was to study if and how inter-individual variability in motor neuron numbers in a small nervous system is compensated. In the stomatogastric nervous system of the lobster Homarus americanus, one group of rhythmically active motor neurons exists in variable copy numbers across individuals. Pyloric (PY) neurons are present in 3 to 5 copies, in rare cases even up to 7. Despite this variability, the relative timing between PY neurons and synaptic partners is highly constrained across individuals. How the variability in numbers of neurons is compensated at the level of the central circuitry has so far eluded us. The consequence of ablating PY neurons has very variable effects on the timing of synaptic partners, suggesting that different individuals may use a different interplay of synaptic and intrinsic neuronal properties to determine relative timing of firing. However, we successfully determined the locus of compensation at the neuromuscular junction. We showed that individual PY’s natural rhythmic activity patterns across animals are independent of the total number of PY neurons present. We also showed that every PY neuron innervated every fiber in PY innervated muscles. Consequently, different numbers of motor neurons are not compensated by differences in the innervation pattern across muscle fibers. Despite different numbers of presynaptic axons, intracellular muscle fiber recordings during ongoing natural PY activity showed no differences in the electrical muscle response. Using single stimulation pulses and only activating one PY neuron did not reveal any differences in the excitatory junction potential (EJP) between animals with different numbers of PY either, neither in amplitude nor time course. In consequence, the compound EJP in response to simultaneous activation of all PY axons was larger in preparations with more PY neurons. However, the muscle response to train stimulation did not differ across animals with different numbers of motor neurons, as animals with fewer PY neurons showed more facilitation over the course of a burst. Therefore, different numbers of motor neurons were compensated at the level of neuromuscular junctions by differences in synaptic dynamics. This suggests that homeostatic long-term regulatory mechanisms can act on short-term synaptic dynamics instead of absolute synaptic strength.
Publications
- (2012) Short-term synaptic plasticity compensates for variability in number of motor neurons at a neuromuscular junction. J. Neurosci. 32:16007-16017
Daur N, Bryan AS, Garcia VJ, Bucher D
