The long term objectives of this proposal are to study the development of intrinsic inhibitory influences on cortical function. Morphologically, synaptogenesis in the cortex proceeds through stages. This series of experiments is designed to study in detail the maturation of function associated with elaboration of intracortical circuitry during early development. The relatively simplified general cortex of the turtle Pseudemys scripta has been selected as a preparation ideally suited for study. The cellular differentiation of the inhibitory interneuron of the turtle and its normal target cell, the cortical pyramidal neuron, will be explored. The timetable of development of inhibitory synapses onto the pyramidal cell will be established along with a detailed characterization of the post synaptic inhibitory receptor, its ontogenesis and topographical distribution through early developmental stages. Methods will include conventional intracellular recording techniques, membrane patch clamp, and the application of monoclonal antibody labels. Since inhibitory control over cortical excitability can play a key role in epileptogenesis, these studies will form a necessary background for the study of epilepsy in the developing cortex.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07NS000887-02
Application #
3078269
Study Section
Neurological Disorders Program Project Review B Committee (NSPB)
Project Start
1984-07-01
Project End
1989-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Blanton, M G; Lo Turco, J J; Kriegstein, A R (1990) Endogenous neurotransmitter activates N-methyl-D-aspartate receptors on differentiating neurons in embryonic cortex. Proc Natl Acad Sci U S A 87:8027-30
Blanton, M G; Lo Turco, J J; Kriegstein, A R (1989) Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortex. J Neurosci Methods 30:203-10
Shen, J M; Kriegstein, A R (1989) The development of bicuculline-induced epileptiform discharges in embryonic turtle cortex. Neurosci Lett 98:184-8
Shen, J M; Huguenard, J R; Kriegstein, A R (1988) Development of GABA responsiveness in embryonic turtle cortical neurons. Neurosci Lett 89:335-41
Schlegel, J R; Kriegstein, A R (1987) Quantitative autoradiography of muscarinic and benzodiazepine receptors in the forebrain of the turtle, Pseudemys scripta. J Comp Neurol 265:521-9
Kriegstein, A R (1987) Synaptic responses of cortical pyramidal neurons to light stimulation in the isolated turtle visual system. J Neurosci 7:2488-92
Kriegstein, A R; Suppes, T; Prince, D A (1987) Cellular and synaptic physiology and epileptogenesis of developing rat neocortical neurons in vitro. Brain Res 431:161-71
Blanton, M G; Shen, J M; Kriegstein, A R (1987) Evidence for the inhibitory neurotransmitter gamma-aminobutyric acid in aspiny and sparsely spiny nonpyramidal neurons of the turtle dorsal cortex. J Comp Neurol 259:277-97
Kriegstein, A R; Connors, B W (1986) Cellular physiology of the turtle visual cortex: synaptic properties and intrinsic circuitry. J Neurosci 6:178-91
Connors, B W; Kriegstein, A R (1986) Cellular physiology of the turtle visual cortex: distinctive properties of pyramidal and stellate neurons. J Neurosci 6:164-77

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