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Sunday, July 19 • 7:00pm - 8:00pm
P79: Frequency-dependent synaptic gain in a computational model of mouse thoracic sympathetic postganglionic neurons

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INFORMATION FOR P79 POSTER PRESENTATION ZOOM MEETING:
Join Zoom Meeting at
https://us02web.zoom.us/j/81765615367?pwd=alplenZxREVZVmJUdnlHa2ROV3c5Zz09
Meeting ID: 817 6561 5367
Password: 9V1TU1

THE ZOOM MEETING WILL BE OPEN 12:30PM - 04:30PM EASTERN DAYLIGHT SAVING TIME (ATLANTA TIME),
 WHICH IS 12:30PM - 04:30PM CENTRAL EUROPEAN SUMMER TIME (BERLIN TIME). IF YOU HAVE TROUBLE ENTERING THE MEETING, EMAIL astrid.prinz@emory.edu

Astrid Prinz, Michael McKinnon, Kun Tian, Shawn Hochman  
Postganglionic neurons in the thoracic sympathetic chain represent the final common output of the sympathetic nervous system. These neurons receive synaptic inputs exclusively from preganglionic neurons located in the spinal cord. Synaptic inputs come in two varieties: primary inputs, which are invariably suprathreshold, and secondary inputs, which exhibit a range of typically subthreshold amplitudes. Postganglionic neurons typically receive a single primary input and a variable number of secondary inputs in what has been described as an “n+1” connectivity pattern. Secondary inputs have often been viewed as inconsequential to cell recruitment due to the short duration of measured synaptic inputs and the relatively low tonic firing rate of preganglionic neurons in vivo. However, recent whole-cell patch clamp recordings reveal that thoracic postganglionic neurons have a greater capacity for synaptic integration than previous microelectrode recordings would suggest. This supports a greater role for secondary synapses in cell recruitment.

We previously created a conductance-based computational model of mouse thoracic postganglionic neurons. In the present study, we have expanded the single-cell model into a network model with synaptic inputs based on whole-cell recordings. We systematically varied the average firing rate of a network of stochastically firing preganglionic neurons and measured the resultant firing rate in simulated postganglionic neurons. Synaptic gain was defined as the ratio of postganglionic to preganglionic firing rate.

We found that for a network configuration that mimics the typical arrangement in mouse, low presynaptic firing rates (<0.1Hz) resulted a synaptic gain close to 1, while firing rates closer to 1Hz resulted in a synaptic gain of 2.5.  Synaptic gain diminished for firing rates higher than ~3Hz. We also determined that synaptic gain linearly increases with the number of secondary synaptic inputs (n) within the range of physiologically realistic presynaptic firing rate. Amplitude of secondary inputs also determines frequency-dependent synaptic gain, with a bifurcation where secondary synaptic amplitude equals recruitment threshold. We further demonstrate that the synaptic gain phenomenon depends on the preservation of passive membrane properties as determined by whole-cell recordings.

One major biological role of the sympathetic nervous system is the regulation of vascular tone in both skeletal muscle and cutaneous structures. The firing rate of muscle vasoconstrictor preganglionic neurons is modulated by the cardiac cycle, while cutaneous vasoconstrictor neurons fire independently of the cardiac cycle. We modulated preganglionic firing rate according to the typical mouse heart rate to determine if cardiac rhythmicity changes the overall firing rate of postganglionic neurons. Cardiac rhythmicity does not appear to have a significant impact on synaptic gain within the physiological range of preganglionic input.

Under normal physiological conditions, the unity gain of sympathetic neurons would lead to faithful transmission of central signals to peripheral targets. However, during episodes of high sympathetic activation, the postganglionic network can amplify central signals in a frequency-dependent manner. These results suggest that postganglionic neurons play a more active role in shaping sympathetic activity than previously thought.

 


Speakers
avatar for Astrid A. Prinz

Astrid A. Prinz

Associate Professor, Department of Biology, Emory University



Sunday July 19, 2020 7:00pm - 8:00pm CEST
Slot 20