The dendrites of many neurons contain voltage-gated channels that turn otherwise passive structures into electrically excitable dendrites. Dendritic excitability enables backpropagation of action potentials from the soma into the dendritic tree and the initiation of spikes in the dendrite and these phenomena play important roles in synaptic integration and in synaptic plasticity. Dendritic excitability has been studied extensively in brain slice preparations and to a lesser extent in anesthetized animals, but little is known about dendritic excitability in awake animals. To understand how ongoing synaptic activity affects synaptic integration and plasticity in vivo, in this project we will directly measure dendritic excitability in awake animals using whole-cell recording and two-photon imaging techniques, using the extent of propagation of action potentials into the dendritic tree as a measure of dendritic excitability. Since these are the first studies to use these high-resolution techniques in awake animals, our studies will provide unprecedented information on dendritic function in awake animals.

Public Health Relevance

The dendrites of many neurons contain voltage-gated channels that play important roles in synaptic integration and in synaptic plasticity, but little is known about dendritic excitability in awake animals, where synaptic integration is performed against a background of ongoing synaptic activity. Here we propose to investigate the effects of ongoing synaptic activity on the dendrites of layer 2/3 neocortical pyramidal neurons in awake rats using whole-cell recording and two-photon imaging techniques. Our studies will be the first to make intracellular measurements of dendritic excitability in awake animals and will therefore provide unprecedented information on dendritic function in awake animals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH085117-02
Application #
7886479
Study Section
Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
Program Officer
Asanuma, Chiiko
Project Start
2009-07-04
Project End
2012-07-31
Budget Start
2010-05-01
Budget End
2012-07-31
Support Year
2
Fiscal Year
2010
Total Cost
$190,625
Indirect Cost
Name
Northwestern University at Chicago
Department
Physiology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Hedrick, Tristan; Waters, Jack (2015) Acetylcholine excites neocortical pyramidal neurons via nicotinic receptors. J Neurophysiol 113:2195-209
Kalmbach, Abigail; Waters, Jack (2014) Modulation of high- and low-frequency components of the cortical local field potential via nicotinic and muscarinic acetylcholine receptors in anesthetized mice. J Neurophysiol 111:258-72
Oh, M Matthew; Oliveira, Fernando A; Waters, Jack et al. (2013) Altered calcium metabolism in aging CA1 hippocampal pyramidal neurons. J Neurosci 33:7905-11
Hedrick, Tristan; Waters, Jack (2012) Effect of temperature on spiking patterns of neocortical layer 2/3 and layer 6 pyramidal neurons. Front Neural Circuits 6:28
Kalmbach, Abigail; Hedrick, Tristan; Waters, Jack (2012) Selective optogenetic stimulation of cholinergic axons in neocortex. J Neurophysiol 107:2008-19
Srivastava, Deepak P; Jones, Kelly A; Woolfrey, Kevin M et al. (2012) Social, communication, and cortical structural impairments in Epac2-deficient mice. J Neurosci 32:11864-78
Hedrick, Tristan; Waters, Jack (2011) Spiking patterns of neocortical L5 pyramidal neurons in vitro change with temperature. Front Cell Neurosci 5:1
Hedrick, Tristan; Waters, Jack (2010) Physiological properties of cholinergic and non-cholinergic magnocellular neurons in acute slices from adult mouse nucleus basalis. PLoS One 5:e11046