Brain function relies on information transfer between neurons at structurally and functionally defined sites called synapses. Considerable effort is directed at understanding the detailed mechanisms underlying synaptic transmission because it is increasingly clear that many diseases of the brain, including neurodevelopmental disorders and the earliest stages of neurodegenerative diseases, are associated with dysregulation of synaptic function. Synaptic transmission is composed of three components including the presynaptic release of neurotransmitter containing vesicles, diffusion of neurotransmitter through the space between neurons, and the activation of receptors that generate a response in the postsynaptic neuron. These events take place on a millisecond time scale, and the timing of each component is tightly controlled to ensure precise and efficient information transfer. Yet transmission is also highly dynamic, showing many types of plasticity in response to natural stimulus patterns. The overall goal of this project is to determine how activity controls the synchrony of neurotransmitter release from the presynaptic terminal, and how this activity-dependent plasticity contributes to the timing of information transfer through the synapse. We will first establish the conditions and mechanisms that control the synchronicity of transmitter release. We will subsequently test physiological consequences of activity dependent asynchronous transmitter release in terms of neural output and postsynaptic Ca2+ signaling. These studies will be conducted in brain slices from mice using voltage and current clamp recordings as well as calcium imaging and pharmacological manipulations. We will use a cerebellar synapse where it is well established that precise timing of synaptic transmission is critical for behaviors such as motor control and motor learning. The results from these studies will provide insight into an important presynaptic mechanism for regulating synaptic transmission that likely plays a role in neural timing throughout the CNS.
The timing of fast synaptic transmission is tightly controlled to ensure precise and efficient information transfer. The overall goal of this project is to determine how activity controls the synchrony of neurotransmitter release from the presynaptic terminal, and how this contributes to the timing of information transfer through the synapse.
|Gonzalez, Jose Carlos; Epps, S Alisha; Markwardt, Sean J et al. (2018) Constitutive and Synaptic Activation of GIRK Channels Differentiates Mature and Newborn Dentate Granule Cells. J Neurosci 38:6513-6526|
|Froula, Jessica M; Henderson, Benjamin W; Gonzalez, Jose Carlos et al. (2018) ?-Synuclein fibril-induced paradoxical structural and functional defects in hippocampal neurons. Acta Neuropathol Commun 6:35|
|Nietz, Angela K; Vaden, Jada H; Coddington, Luke T et al. (2017) Non-synaptic signaling from cerebellar climbing fibers modulates Golgi cell activity. Elife 6:|
|Adlaf, Elena W; Vaden, Ryan J; Niver, Anastasia J et al. (2017) Adult-born neurons modify excitatory synaptic transmission to existing neurons. Elife 6:|
|Erlenhardt, Nadine; Yu, Hong; Abiraman, Kavitha et al. (2016) Porcupine Controls Hippocampal AMPAR Levels, Composition, and Synaptic Transmission. Cell Rep 14:782-794|
|Dieni, Cristina V; Panichi, Roberto; Aimone, James B et al. (2016) Low excitatory innervation balances high intrinsic excitability of immature dentate neurons. Nat Commun 7:11313|
|Rudolph, Stephanie; Tsai, Ming-Chi; von Gersdorff, Henrique et al. (2015) The ubiquitous nature of multivesicular release. Trends Neurosci 38:428-38|
|Coddington, Luke T; Nietz, Angela K; Wadiche, Jacques I (2014) The contribution of extrasynaptic signaling to cerebellar information processing. Cerebellum 13:513-20|
|Chancey, Jessica H; Poulsen, David J; Wadiche, Jacques I et al. (2014) Hilar mossy cells provide the first glutamatergic synapses to adult-born dentate granule cells. J Neurosci 34:2349-54|
|Overstreet-Wadiche, Linda; Wadiche, Jacques I (2014) Good housekeeping. Neuron 81:715-7|
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