Differential effects of cortical neurotrophic factors on development of lateral geniculate nucleus and superior colliculus neurons: anterograde and retrograde actions

Abstract

Neurotrophins strongly affect visual system development and plasticity. However, the mode of delivery and targets of neurotrophin action are still under debate. For instance, cortical NT-4/5 (neurotrophin 4/5; Ntf4/5) was shown to rescue lateral geniculate nucleus (LGN) neurons from monocular deprivation-induced atrophy suggesting a retrograde action on thalamic afferents. It is still unclear whether LGN neurons respond to NT-4/5 and other neurotrophins during development in animals with normal vision. We now show that infusions of NT-4/5 and NGF (nerve growth factor) into visual cortex at the onset and the peak of the critical period accelerated LGN neuron growth. BDNF (brain-derived neurotrophic factor) was ineffective. The effects of neurotrophin on LGN development were clearly dissociated from the effects at cortical level because soma growth of cortical layer IV and VI neurons was strongly promoted by BDNF. NT-4/5 was only effective at the onset, but no longer at the peak of the critical period suggesting a switch in neurotrophin dependency for these cortical cell classes. To dissociate retrograde and anterograde effects of the TrkB ligands, we analyzed the stratum griseum superficiale (SGS) of the superior colliculus, a target of visual cortical efferents. Indeed, TrkB-expressing inhibitory SGS neurons responded to cortical NT-4/5 infusion with somatic growth. Strikingly, the TrkB-expressing excitatory tectothalamic calbindin neurons in the SGS did not respond. This demonstrated for the first time a selective cell type-specific anterograde action of NT-4/5 and suggested for the LGN that anterograde as well as retrograde effects contribute to soma size regulation. Strikingly, cortical infusion of the cytokine LIF, which affects development of visual cortex neurochemical architecture, transiently inhibited growth of neurons in LGN,cortical layer IV and VI and SGS. In summary, the study presents three important results. First, central neurons regulate soma size development in an age-and ligand-specific fashion. Second, NT-4/5 and NGF accelerate LGN development in rats with normal vision while LIF delays growth. Third,anterogradely transported NT-4/5 effectively promotes neuronal maturation. These differential actions on subcortical neurons may contribute to the different effects of neurotrophins on visual system development and plasticity.

GABAC receptor subunit mRNA expression in the rat superior colliculus is regulated by calcium channels, neurotrophins, and GABAC receptor activity

“…The expression of BDNF mRNA and protein has been described in the superficial layers of the SC (Pollock et al, 2001). TrkB and TrkC receptors (Vizuete et al, 2001;Wahle et al, 2003) and the low-affinity p75 receptor (Harvey, 1994) have been described, and we have verified the presence of TrkA mRNA at 10 and 20 DIV (data not shown). OTCs of the SC were treated from 0-10 and 0-20 DIV with either NGF, NT3, NT4, or BDNF (50 ng/ml).…”

“…To rule out artefacts due to a malformation of the layers in vitro, we verified the presence of the superficial layers in these cultures with in situ hybridization against GAD65 mRNA expressed by GABAergic neurons. These neurons are concentrated in the superficial layers in the SC in vivo (Mize, 1992;Wahle et al, 2003), and GAD65 mRNA expressing neurons were also concentrated dorsally in SC cultures (Fig. 1C).…”

Normal eye-specific patterning of retinal inputs to murine subcortical visual nuclei in the absence of brain-derived neurotrophic factor

“…In the present study, we find normal eye-specific patterning whether BDNF expression is eliminated or reduced throughout the body or only in the central nervous system (CNS). We do note, however, that elimination of expression might be compensated for by other trkB ligands such as NT-4 (Riddle et al, 1995;Bosco & Linden, 1999;Fan et al, 2000), although NT-4 may be cortically derived (Wahle et al, 2003).…”

Postnatal Generation of Neurons in the Ventrobasal Nucleus of the Rat Thalamus

“…It is unclear whether the BDNF is transported through corticothalamic or thalamocortical pathways or both, although the data cited above strongly implicate corticothalamic projections. After all, neurotrophins can act through anterograde Miller, 1995, 2000;Wahle et al, 2003) and retrograde (DiStefano et al, 1992;Crockett et al, 2000;Wahle et al, 2003) mechanisms. The end of the second wave of neuronogenesis is punctuated by the loss of the neurotrophin receptors, both p75 and trk, during the third postnatal week.…”