Weak and straddling secondary nicotinic synapses can drive firing in rat sympathetic neurons and thereby contribute to ganglionic amplification

Abstract

Interactions between nicotinic excitatory postsynaptic potentials (EPSPs) critically determine whether paravertebral sympathetic ganglia behave as simple synaptic relays or as integrative centers that amplify preganglionic activity. Synaptic connectivity in this system is characterized by an n + 1 pattern of convergence, where each ganglion cell receives one very strong primary input and a variable number (n) of weak secondary inputs that are subthreshold in strength. To test whether pairs of secondary nicotinic EPSPs can summate to fire action potentials (APs) and thus mediate ganglionic gain in the rat superior cervical ganglion, we recorded intracellularly at 34°C and used graded presynaptic stimulation to isolate individual secondary synapses. Weak EPSPs in 40 of 53 neurons had amplitudes of 0.5–7 mV (mean 3.5 ± 0.3 mV). EPSPs evoked by paired pulse stimulation were either depressing (n = 10), facilitating (n = 9), or borderline (n = 10). In 15 of 29 cells, pairs of weak secondary EPSPs initiated spikes when elicited within a temporal window <20 ms, irrespective of EPSP amplitude or paired pulse response type. In six other neurons, we observed novel secondary EPSPs that were strong enough to straddle spike threshold without summation. At stimulus rates <1 Hz straddling EPSPs appeared suprathreshold in strength. However, their limited ability to drive firing could be blocked by the afterhyperpolarization following an AP. When viewed in a computational context, these findings support the concept that weak and straddling secondary nicotinic synapses enable mammalian sympathetic ganglia to behave as use-dependent amplifiers of preganglionic activity.

Virtual leak channels modulate firing dynamics and synaptic integration in rat sympathetic neurons: implications for ganglionic transmission in vivo

“…; Bratton et al . ; Rimmer & Horn, ). To obtain a fuller picture, we also measured EPSPs evoked by graded presynaptic stimulation of the cervical sympathetic trunk.…”

“…Although support for the gain hypothesis comes from computational simulations, together with microelectrode recordings from isolated intact ganglia and dynamic clamp studies of bullfrog neurons (Karila & Horn, ; Wheeler et al . ; Kullmann & Horn, ; Rimmer & Horn, ; Kullmann & Horn, ), another critical test would be to analyse synaptic activity in living animals. Such experiments are extremely difficult and to date have yielded contradictory results.…”

On the Number of Preganglionic Neurons Driving Human Postganglionic Sympathetic Neurons: A Comparison of Modeling and Empirical Data

“…We know from studies in the anesthetized rat that some postganglionic neurons in the superior cervical ganglion, which supply many different tissues, are driven by two (rarely three) preganglionic neurons with “strong” synapses, but that most are driven by only one (McLachlan et al, 1997, 1998; Li and Horn, 2006; Rimmer and Horn, 2010). Moreover, close temporal coincidence of EPSPs from two preganglionic neurons with “weak” synapses can bring the postganglionic neuron to threshold (Rimmer and Horn, 2010).…”

“…Moreover, close temporal coincidence of EPSPs from two preganglionic neurons with “weak” synapses can bring the postganglionic neuron to threshold (Rimmer and Horn, 2010). Like those in the superior cervical ganglion, most postganglionic neurons recorded from a lumbar sympathetic ganglion in the rat – the majority of which are vasoconstrictor in function – are driven by one “primary” preganglionic neuron, but inputs from two (or rarely three) “secondary” preganglionic neurons can occasionally contribute to the firing of a single postganglionic neuron (Bratton et al, 2010).…”

Functional organization of autonomic neural pathways

“…The remaining inputs are usually subthreshold for action potential generation. Their main function seems to be to set the gain of ganglionic transmission 28 . Alternatively they may represent inputs from a secondary central pathway that is effective only at high levels of convergent activity 28 or under pathological conditions where their influence is magnified 27 …”