Selective Stabilization of Synaptic Inputs onto Motoneurons by Postsynaptic trkB Receptors Open Access

Zhu, Xiya (2013)

Permanent URL: https://etd.library.emory.edu/concern/etds/bn9997188?locale=en
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Abstract

Following peripheral nerve injury, synaptic terminals withdraw from the cell bodies of motoneurons in the spinal cord in a process known as synaptic stripping. Stripping is thought to be the result of a decrease in the release of brain derived neurotrophic factor (BDNF) from injured motoneurons. This decrease in binding of motoneuron BDNF to trkB receptors on synaptic terminals results in their withdrawal, implying that this retrograde signaling maintains synaptic contacts. However, trkB receptors are plentiful on BOTH motoneurons and on synapses onto them. We hypothesize that the motoneuron trkB receptors play a role in the maintenance of synaptic inputs onto motoneurons. In male and female mice in which the gene for trkB was knocked out selectively in a subset of motoneurons, the proportion of the motoneuron somata contacted by excitatory (VGLUT1+, VGLUT2+) and inhibitory (GAD67+, glycine+) synaptic inputs was measured. Results from wild type (WT) and trkB knockout (KO) cells were compared. Simply eliminating expression of the trkB receptor in motoneurons resulted in a significant reduction in VGLUT2+, GAD67+, and glycine+ synaptic contacts but had no effect on the magnitude of excitatory VGLUT1+ synaptic inputs. The magnitude in the reduction in synaptic inputs was nearly twice as great for inputs immunoreactive for GAD67 as for other inputs. The reduction in synaptic coverage by VGLUT2 and glycine was much greater in males than in females, whereas no sex difference was found in reduction of GAD67+ contacts. Thus, expression of trkB in motoneurons plays an integral role in the maintenance of inhibitory synapses and this role is different in males and females. Motoneuron BDNF, acting in an autocrine/ paracrine manner through these postsynaptic receptors, could have a self amplifying effect to stabilize synaptic terminals.

Table of Contents

I. Introduction.....................................................................................................................1

II. Methods..........................................................................................................................5

Animals.................................................................................................................................5

Retrograde Labeling................................................................................................................5

Immunohistochemistry............................................................................................................6

Image Analysis.......................................................................................................................7

Statistics...............................................................................................................................8

III. Results.........................................................................................................................10

VGLUT1+ synapses in trkB-KO mice.........................................................................................11

VGLUT2+ synapses in trkB-KO mice.........................................................................................11

GAD67+ synapses in trkB-KO mice..........................................................................................12

Glycine+ synapses in trkB-KO mice.........................................................................................13

Difference in percent synaptic coverage by inhibitory vs. excitatory terminals...............................15

IV. Discussion....................................................................................................................17

V. Figures

Figure 1. KO motoneuron with VGLUT1+ synaptic terminals and plot profile................................. 9

Figure 2. Reduction in synaptic coverage after elimination of motoneuron trkB receptors............... 10

Figure 3. Cumulative frequency plot of percent synaptic coverage .............................................. 14

Figure 4. Synaptic terminals withdrawn in motoneuron-specific trkB KO mice............................... 15

Figure 5. Difference in mean percent synaptic coverage............................................................ 16

Figure 6. BDNF-trkB self-amplification pathway ....................................................................... 22

VI. Tables.......................................................................................................................... 23

Table 1. Groups of mice used in the study

Table 2. Antibodies used in immunohistochemistry staining

Table 3. Results of one way analysis of variance

VII. References Cited.........................................................................................................24

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