Frequency-Dependent Release of Substance P Mediates Heterosynaptic Potentiation of Glutamatergic Synaptic Responses in the Rat Visual Thalamus

Abstract

To investigate the interaction between peptides and glutamatergic synapses in the dorsal thalamus, we compared the frequency-dependent plasticity of excitatory postsynaptic potentials (EPSPs) in the tectorecipient zone of rodent lateral posterior nucleus (LPN), which is densely innervated by axons that contain the neuromodulator substance P (SP). Immunocytochemistry and confocal and electron microscopy revealed that neurokinin 1 (NK1) receptors are distributed on the dendrites of LPN cells, whereas SP is contained in axons originating from the superior colliculus (SC) and is reduced following SC lesions. In vitro whole cell recordings in parasagittal slices revealed that stimulation of the SC or optic radiations (corticothalamic axons [CTXs]) evoked LPN EPSPs that increased in amplitude with increasing stimulation intensity, suggesting convergence. With 0.5- to 10-Hz stimulus trains, CTX EPSP amplitudes displayed frequency-dependent facilitation, whereas SC EPSP amplitudes were unchanged. High-frequency SC stimulation (100 Hz for 0.5 s), or bath application of SP, resulted in gradual increases in both SC and CTX EPSP amplitudes to twofold or greater above baseline within 15-20 min poststimulation/application. This enhancement correlated with increases in input resistance and both the potentiation and resistance change were abolished in the presence of the NK1 antagonist L-703,606. These results indicate that SP is released when SC-LPN neurons fire at high frequency and SP acts postsynaptically via NK1 receptors to potentiate subsequent LPN responses to both cortical and tectal inputs. We suggest that the SP-mediated potentiation of synaptic responses may serve to amplify responses to threatening objects that move across large regions of the visual field.

Kisspeptin inhibits a slow afterhyperpolarization current via protein kinase C and reduces spike frequency adaptation in GnRH neurons

“…Although single action potential-induced calcium influx is enough to spark the release of classical transmitters, burst firing or tetanic stimulation is required for the release of neuropeptides such as vasopressin, oxytocin, substance P, and atrial natriuretic factor (3,34,49). Previous studies have shown that kisspeptin robustly depolarizes and increases the firing of GnRH neurons through a combination of activating TRPC channels and attenuating K ir conductances (31,42,58,59).…”

Signal processing in the tectothalamic pathway.

“…This conclusion is also based on comparisons to our previous study of EPSPs elicited by stimulation of tectothalamic axons in the rat. Tectothalamic projections in the rodents are nontopographic (Mooney et at, 1984) and EPSP amplitudes remain stable at stimulation frequencies of up to 20Hz (Masterson et at, 2010). The lack of short-term frequency-dependent plasticity in the rat tectothalamic pathway is similar to that exhibited by the slower latency, smaller amplitude tectopulvinar EPSPs of the tree shrew.…”

Circuits for active vision : parallel tectothalamocortical visual pathways in the mouse.

“…Similar examples of driver-like convergence illustrate the complexity of thalamic organization. The dorsal thalamus may be divided not only into "first order" (driven by ascending peripheral input) or "higher order" (driven by descending cortical input) nuclei (Guillery and Sherman, 2002), but also "second order" nuclei driven by convergent, ascending inputs (Kelly et al, 2003;Smith et al, 2007;Chomsung et al, 2008;Masterson et al, 2009Masterson et al, , 2010, or nuclei that contain unique combinations of ascending and descending driver-like inputs (Baldauf et al, 2005;Rovo et al, 2012;Groh et al, 2014). Such diversity may dramatically increase the computational capabilities of the thalamus, reflecting its essential roles in sensory, motor, and sensory-motor circuits.…”

“…As schematically illustrated in Figure 11, this homology is based to a large extent on commonalities in the projections of the superficial (visual) layers of the superior colliculus (SC), or optic tectum, to the primate pulvinar nucleus, rodent/carnivore LPN, and avian nucleus rotundus (Harting et al, 1973b;Robson and Hall, 1977;Berson and Graybiel, 1978;Mooney et al, 1984;Takahashi, 1985;Abramson and Chalupa, 1988;Luppino et al, 1988;Hutsler and Chalupa, 1991;Villeneuve and Casanova, 2003;Kelly et al, 2003;Chomsung et al, 2008;Masterson et al, 2009Masterson et al, , 2010Baldwin et al, 2011;Wei et al, 2011b;Fredes et al, 2012;Baldwin et al, 2013). Because of these similarities, we will refer to this region of the mouse thalamus as the pulvinar nucleus.…”

“…However, as reviewed in Chapter III, Masterson et al (2009Masterson et al ( , 2010 proposed that tectorecipient subdivisions of the pulvinar nucleus should be considered as "second order" rather than "first order" or "higher order", because tectal terminals do not exhibit the characteristic of either the "drivers" or "modulators" defined by Sherman and Guillery 1998. In addition, as described in Chapter II, certain regions of the dLGN also do not fit the criteria or first or higher order nuclei.…”