Patrick J. Mueller and Nicholas A. Mischel
Many previous studies have shown
that sedentary conditions can result in enhanced nerve activity following
activation of the rostral ventrolateral medulla (RVLM). This means that there
is some type of mechanism that differs between active and sedentary animals in
terms of the excitation and inhibition that occurs in the RVLM. The RVLM is
primarily regulated by glutamate, an excitatory neurotransmitter, and GABA, an
inhibitory neurotransmitter. This study was trying to determine how the
glutamate could directly excite the RVLM, and the effects that blocking the
GABA pathway may have on the response to glutamate. The hypothesis was that
sedentary conditions would enhance sympthoexcitatory response to direct
activation of the RVLM, with the responses increasing further by blocking tonic
GABAergic transmission.
The methods of the experiment were
similar to our microinjection protocols in terms of exposing the RVLM and
recording nerve activity and blood pressure. The first protocol involved
injection 1, 10, and 100mM concentrations of glutamate into the RVLM while
recording the blood pressure, heart rate, and lumbar sympathetic nerve activity
(LSNA). The second protocol administered a GABA receptor blocker called
bicuculline before glutamate injections were performed. The glutamate was
injected 5, 10, 15, 30, and 45 minutes after the bicuculline was administered
to investigate the changes in nerve activity after certain periods of time. The
third protocol was a control section in which glutamate response was tested in
the presence and absence of artificial cerebral spinal fluid.
In protocol one, responses to
varying concentrations of direct glutamate administration did not differ
between the sedentary and active animals. This is because heart rate responses
were small and increases in LSNA also did not differ significantly between the
active and sedentary animals. In protocol two, the initial injections of
bicuculline increased the baseline blood pressure, heart rate, and LSNA in both
the active and sedentary animals prior to any glutamate being injected. The
increases did not differ significantly between the two groups. The glutamate
injection responses at 5 and 15 minutes after the bicuculline was administered
were greatly enhanced in the sedentary animals compared to the physically
active animals. These enhancements were observed as increases in mean arterial
pressure, however, were no longer observed by the 30- and 45-minute marks.
Increases in LSNA were enhanced at the 5-, and 15-minute marks as well, however
there was not a significant difference between the sedentary and active
groups. Once again, these effects were no longer observed at 30 and 45
minutes. This suggests that there was full recovery from bicuculline within the
time course mentioned. Protocol three showed that responses to glutamate
injections at different time points after injection of the bicuculline vehicle
(aCSF) did not differ significantly from the control microinjections. In
addition, responses to the repetitive microinjections did not differ
significantly between the active and sedentary groups.
Overall, there were results that
both confirmed and opposed the hypothesis. The hypothesis was confirmed in that
there was enhancement in the response to glutamate in sedentary animals after
the GABA receptor block was administered in the RVLM. However, the LSNA
responses did not differ between groups under direct glutamate activation nor
under GABA receptor blockade conditions.
Based on the results, the paper
determined several new findings that helped distinguish the effects of
sedentary verses active conditions on nerve activity and blood pressure. First,
sedentary conditions enhance GABAergic control of glutamate-sensitive neurons
in the RVLM that regulate blood pressure. Second, sedentary conditions increase
nerve activity when glutamate is administered in the absence of GABAergic
modulation. Lastly, LSNA does not control the responses recorded in animals
after GABA receptor blockers were administered.
This study helps us to possibly
think about what other protocols we may want to add to the microinjection
experiments. We could find other drugs that block glutamate or GABA responses
in the RVLM and then see what effects present themselves when glutamate and
GABA doses are given in the active and sedentary animals.
-Lyndsey M.
