Activity-Dependent Regulation of Substance P Expression and Topographic Map Maintenance by a Cholinergic Pathway

Abstract

We have assessed the role of activity in the adult frog visual system in modulating two aspects of neuronal plasticity: neurotransmitter expression and topographic map maintenance. Chronic treatment of one tectal lobe with the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione decreased the percentage of substance P-like immunoreactive (SP-IR) tectal cells in the untreated lobe while disrupting topographic map formation in the treated one. Treatment with the NMDA receptor antagonist d-(-)-2-amino-5-phosphonovaleric acid (d-AP-5) disrupted the topographic map but had no affect on SP-IR cells. These results indicate that maintenance of the topographic map is dependent on direct input from the glutamatergic retinal ganglion cells, whereas substance P (SP) expression is being regulated by a pathway that relays activity from one tectal lobe to the other. Such a pathway is provided by the cholinergic nucleus isthmi, which is reciprocally connected to the ipsilateral tectum and sends a projection to the contralateral one. Mecamylamine and atropine, antagonists of nicotinic and muscarinic receptors, respectively, were used together to block all cholinergic activity or alone to block receptor subclass activity. All three treatments decreased SP expression and disrupted the topographic map in the treated tectal lobe. We conclude that both SP expression and topographic map maintenance in the adult optic tectum are activity-dependent processes. Although our results are consistent with the maintenance of the topographic map through an NMDA receptor-based mechanism, they suggest that SP expression is regulated by a cholinergic interaction that depends on retinal ganglion cell input only for its activation.

Evidence for an Instructive Role of Retinal Activity in Retinotopic Map Refinement in the Superior Colliculus of the Mouse

“…This could be because the pharmacological intervention was imperfect or because postsynaptic ␤2 receptors contribute to the KO phenotype. In fact, some have argued for the LGN that retinal waves are merely permissive (Huberman et al, 2002(Huberman et al, , 2003, but not instructive (Shatz and Stryker, 1988;Cook et al, 1999), in the process of RGC axon refinement, and the lack of refinement is attributable to the absence of ␤2 receptors in the target, in which nAChRs positively modulate visual response (Tu et al, 2000). Definitive resolution of this issue awaits the development of region (retina or LGN/ SC)-specific knock-outs of the ␤2 receptor in mice.…”

“…We also observed a decrease in the peak firing rate of collicular neurons in the ␤2 mutants. This suggests that individual inputs to collicular neurons are weaker, but it could also reflect a decrease in the peak firing rate of RGCs in ␤2 mutants or the absence of positive modulation by presynaptic nAChRs in the colliculus (Tu et al, 2000). The enlarged and sometimes patchy RFs observed in juvenile ␤2 Ϫ/Ϫ mice are similar to those observed in the immature LGN (Tavazoie and Reid, 2000) and SC (Carrasco et al, 2003) and the disordered retinotopic maps in adult ␤2 Ϫ/Ϫ mice revealed with optical imaging techniques (Mrsic-Flogel et al, 2005), further suggesting that ␤2 Ϫ/Ϫ RFs are poorly refined.…”

Homeostatic activity-dependent paradigm for neurotransmitter specification

“…19 The appearance of the appropriate transmitters is essential 20 cal activity and calcium (Ca 2+ ) influx also play a key role. 27 Here we summarize investigations of the role of activity in 28 transmitter specification, assembling evidence from studies 29 of classical and peptide transmitters and from embryonic and 30 mature nervous systems that suggests that the role of activity 31 in transmitter specification is geared toward homeostasis. We [10].…”

The effects of nicotinic and muscarinic receptor activation on patch-clamped cells in the optic tectum of rana pipiens

“…Such a facilitatory effect, dependent upon cholinergic activity, has been directly demonstrated in the goldfish (King and Schmidt, 1991). Effects on visual plasticity have also been demonstrated: cholinergic activity both maintains the topographic map of visual space created in the tectum and regulates substance P expression in a population of tectal cells (Tu et al, 2000).The optic tectum of the frog contains both nicotinic and muscarinic cholinergic receptors (Sargent et al, 1989;Birdsall et al, 1980;Butt et al, 2000Butt et al, , 2001) but knowledge of the physiological consequences of their activation is incomplete. Assessments of the effects of nicotinic receptor activation have focused on a facilitation of glutamate release from retinal ganglion cell terminals (Titmus et al, 1999;Kuras and Gutmaniene, 2001) while muscarinic receptors have been associated with tectal cell membranes following an enhancement of single unit recordings in response to ACh microiontophoresis (Fite and Wang, 1986).…”