Adam Carter

Cellular Neurophysiology

Many neurons in the mammalian brain receive excitatory synapses onto their dendrites at small membrane protrusions known as spines. In active neural circuits, a continual barrage of inputs arrives at multiple spines distributed throughout the dendritic tree. Different types of inputs interact with each other to shape neuronal firing properties and trigger synaptic plasticity.

Many questions remain about neurons process their inputs during natural activity patterns. For example, what kinds of electrical and biochemical signals are generated in spines and dendrites? How do these signals depend on the number, distribution and type of synaptic inputs? Which receptors and channels mediate these signals and how are they altered by neuromodulation? The goal of my lab is to begin to answer these questions and thereby gain a better understanding of how neurons function in the brain. Ultimately, this work will also help us to understand neuronal dysfunction in diseases.

The primary techniques in the lab are electrophysiology and 2-photon microscopy in acute brain slices. Whole-cell recordings allow us to measure evoked currents and potentials at the soma. At the same time, we can fill neurons with fluorescent dyes to image their morphology or measure biological signals. The properties of 2-photon microscopy permit us to image neurons within brain slices at high spatial and temporal resolution. With this approach, we can view stretches of dendrites and individual spines and measure local calcium signals. We can also use 2-photon microscopy to photo-release glutamate at spines, mimicking defined patterns of synaptic inputs.

As a complementary approach, we use in vivo viral infection to label different neurons with fluorescent proteins. This allows us to determine how neurons are connected and where synapses are located in dendrites. We use a similar approach to introduce genetic indicators and effectors into neurons, permitting us to monitor and control their activity without using whole-cell recordings.

Representative Publications

Carter, A.G., and Regehr, W.G. (2000). Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse. J. Neurosci. 20(12): 4423-4434.

Carter, A.G., Vogt, K.E., Foster, K.A., and Regehr, W.G. (2002). Assessing the role of calcium-induced calcium release in short-term presynaptic plasticity at excitatory central synapses. J. Neurosci. 22(1): 21-28.

Kreitzer, A.K., Carter, A.G., and Regehr, W.G. (2002). Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron 34: 787-796.

Carter, A.G., and Regehr, W.G. (2002). Quantal events shape cerebellar interneuron firing. Nature Neuroscience. 5: 1309-1318.

Carter, A.G., and Sabatini, B.L. (2004). State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons. Neuron 44: 483-493.

Crowley, J.J., Carter, A.G., and Regehr, W.G. (2007). Fast Vesicle Replenishment and Rapid Recovery from Desensitization at a Single Synaptic Release Site, J. Neurosci. 27(20): 5448-5460.

Carter, A.G., Soler-Llavina, G.J., and Sabatini, B.L. (2007). Timing and Location of Synaptic Inputs Determine Modes of Subthreshold Integration in Striatal Medium Spiny Neurons, J. Neurosci. 27(33): 8967-8977.