Uncovering the Cellular and Molecular Mechanisms of Synapse Formation and Functional Specificity Using Central Neurons of Lymnaea stagnalis.

All functions of the nervous system are contingent upon the precise organization of neuronal connections that are initially patterned during development, and then continually modified throughout life. Determining the mechanisms that specify the formation and functional modulation of synaptic circuitry are critical to advancing both our fundamental understanding of the nervous system as well as the various neurodevelopmental, neurological, neuropsychiatric, and neurodegenerative disorders that are met in clinical practice when these processes go awry. Defining the cellular and molecular mechanisms underlying nervous system development, function, and pathology has proven challenging, due mainly to the complexity of the vertebrate brain.

A novel bio-mimicking, planar nano-edge microelectrode enables enhanced long-term neural recording.

Our inability to accurately monitor individual neurons and their synaptic activity precludes fundamental understanding of brain function under normal and various pathological conditions. However, recent breakthroughs in micro- and nano-scale fabrication processes have advanced the development of neuro-electronic hybrid technology. Among such devices are three-dimensional and planar electrodes, offering the advantages of either high fidelity or longer-term recordings respectively.

Effect of planar microelectrode geometry on neuron stimulation: finite element modeling and experimental validation of the efficient electrode shape.

Background: Microelectrode arrays have been used successfully for neuronal stimulation both in vivo and in vitro. However, in most instances currents required to activate the neurons have been in un-physiological ranges resulting in neuronal damage and cell death. There is a need to develop electrodes which require less stimulation current for neuronal activation with physiologically relevant efficacy and frequencies.

Trophic factor-induced activity 'signature' regulates the functional expression of postsynaptic excitatory acetylcholine receptors required for synaptogenesis.

Highly coordinated and coincidental patterns of activity-dependent mechanisms ("fire together wire together") are thought to serve as inductive signals during synaptogenesis, enabling neuronal pairing between specific sub-sets of excitatory partners. However, neither the nature of activity triggers, nor the "activity signature" of long-term neuronal firing in developing/regenerating neurons have yet been fully defined. Using a highly tractable model system comprising of identified cholinergic neurons from Lymnaea, we have discovered that intrinsic trophic factors present in the Lymnaea brain-conditioned medium (CM) act as a natural trigger for activity patterns in post- but not the presynaptic neuron.