The microscopic structure of the NC inside is also quite different from that of the empty capsid

sting that it may serve a general role in synaptic organization. Underscoring the functional importance of LRP4, its perturbation in excitatory ORNs abrogated olfactory attraction behavior. The suppression of the behavioral phenotype by reducing presynaptic inhibition onto ORNs further suggests that a proper level of excitatory drive is important for functional circuit output. To mediate both morphological and behavioral effects, LRP4 likely functions through SRPK79D, a conserved SR-protein kinase whose loss-of-function phenotypes resemble those of lrp4, whose synaptic localization depends on LRP4, who interacts genetically with and is physically in proximity to LRP4, and whose overexpression suppresses the phenotypes associated with loss of lrp4. LRP4 as a synaptic regulator that distinguishes excitatory from inhibitory presynaptic terminals Coordination of excitation and inhibition is critical to proper circuit function. Imbalances in excitation and inhibition lead to epileptic states and social MG516 dysfunction, and may also underlie many autism spectrum disorders. The mechanisms that maintain this balance are incompletely understood, though likely involve multiple aspects including the number of each type of neuron, their firing rates, release probabilities, synaptic strength, and neurotransmitter receptor sensitivities. Such regulation likely requires distinguishing excitatory from inhibitory neurons at both pre- and postsynaptic levels. Excitatory and inhibitory synapses are identified postsynaptically by distinct neurotransmitter receptor, scaffolding protein, and adhesion molecule repertoires. Postsynaptic factors like Neuroligin 2, Gephyrin, and Slitrk3 organize inhibitory GABAergic synapses while LRRTMs organize excitatory synapses. Thus, postsynaptic regulation can occur by differential modulation PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19828299 of these factors. Little is known, however, about the presynaptic identifiers of excitatory versus inhibitory neurons. Recent work identified Punctin / MADD-4 as a determinant of excitatory versus inhibitory neuromuscular synapses in C. elegans, though as a secreted factor that functions via postsynaptic interaction . Further, Glypican4 can localize to excitatory presynaptic terminals and interact with LRRTM4 but its synaptogenic activity is also provided by astrocytes and thus is not neuronal specific. Proteomic comparisons suggest few differences beyond those pertaining to neurotransmitter synthesis enzymes and transporters. But these components may not be sufficient to distinguish presynaptic excitatory from inhibitory neurons. In the Drosophila olfactory system, for example, glutamate can be inhibitory when its postsynaptic partners express glutamate-gated chloride channels. This suggests that pre- and postsynaptic regulators may exist to distinguish excitatory and inhibitory synapses, though it is unclear what those presynaptic regulators might be. Our data suggests that LRP4 may be a candidate presynaptic organizer specific for excitatory connections. LRP4 is expressed in a subset of excitatory cholinergic neurons, excluded from inhibitory GABAergic neurons, and expressed in a subset of glutamatergic neurons that may be excitatory or inhibitory. Though we cannot rule out inhibitory neuron expression in the case of the glutamatergic subset, the phenotypes associated with LRP4 perturbation are consistent with an excitatory neuron-specific role. Thus, LRP4 may not only serve an identifying role at excitatory synapses, but also a funct