Short term plasticity between hippocampal pyramidal neurons / Brian N. Johnson.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Johnson, Brian N.

Contributor:

Dichter, Marc, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

Neurosciences.

Academic Dissertations as Topic.

Medical Subjects:

Neurosciences.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

Physical Description:

xi, 145 pages : illustrations (some color) ; 29 cm

Production:

2003.

Summary:

Paired pulse facilitation (PPF) is one of the most fundamental forms of synaptic plasticity, and is thought to be critically important for information processing at synapses throughout the brain. In the results reported here, pairs of EPSCs (at interstimulus intervals from 50--1000 msec) were recorded from CA1 neurons evoked either by direct activation of a simultaneously recorded CA3 neuron or by extracellular "minimal stimulation" of the Schaffer collateral pathway, as a means of assessing short term synaptic plasticity. On average, very little PPF was seen with dual cell recordings, although at the level of individual cells PPF was seen. Minimal stimulation produced significantly more PPF, due to a reduction of "failures" on the second of two stimuli. To test the hypothesis that increases in axonal activation contributed to the PPF seen during minimal stimulation, we evoked antidromic action potentials in CA3 pyramidal cells using a Schaffer collateral stimulation protocol similar to that used during the minimal stimulation experiments. Dramatic facilitation of axonal activation was observed during paired pulse stimulation. Our data indicate that many, if not most, synapses in the CA3-CA1 pathway do not demonstrate PPF and that the significant overestimate of PPF seen with the minimal stimulation paradigm may be due in large part to enhanced axonal excitability.

We also tested the hypothesis that synaptic facilitation plays an important role in the development of spontaneous epileptiform activity. EGTA-AM was employed to block short term plasticity at excitatory synapses. Using non-minimal pathway stimulation of the Schaffer collaterals and recording field potentials from the CA1 stratum radiatum, we found that brief treatment with EGTA-AM had no effect on the first response to a pair of stimuli, but significantly reduced PPF of the second response. After loading the cells with EGTA, spontaneous bicuculline-induced epileptiform discharges almost completely disappeared, although interictal discharges could still be evoked with pathway stimulation, especially on the second of two stimuli. These results support the hypothesis that short term plasticity contributes to the development of spontaneous epileptiform activity, but that other forms of facilitation (e.g. axonal) may play a role in evoked epileptiform activity.

Notes:

Adviser: Marc Dichter.

Thesis (Ph.D. in Neuroscience) -- University of Pennsylvania, 2003.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 3095893.

OCLC:

244973197