Developmental changes of neurotrophin mRNA expression in the layers of rat visual cortex

Abstract

Neurotrophins are essential factors for the structural, neurochemical and functional maturation of the brain including developmental and adult plasticity. Northern blots and polymerase chain reaction revealed the expression of neurotrophin 4 (NT4), neurotrophin 3 (NT3), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the cortex. The cellular producers of NT3 and BDNF have been characterized by anatomical methods as being mostly pyramidal, and the tyrosine kinase B (TrkB) receptor is expressed by many cortical neurons. However, these methods have so far failed to identify the cells producing NT4 and NGF mRNA. These factors are much lower in expression than, e.g. BDNF, and apparently remain below detection levels of in situ hybridization. Given their specific actions on cell types and afferent systems, knowledge about the producing cell types is highly desirable. To narrow down on the producing cell types, we quantified by reverse transcriptase-polymerase chain reaction (RT-PCR) the developmental changes of BDNF, NT3, NT4, NGF and TrkB mRNA expression in total visual cortex lysates, and in the cortical layers dissected by tangential cryostat sectioning. We found dramatic changes in laminar expression of NT3 and NGF, mild changes of NT4, and no changes of BDNF and TrkB mRNA. For instance, NT3 is important early on for thalamocortical axons, and we found transient peaks of NT3 mRNA expression first in layer VI, then in layer IV. NT4 mRNA was in layers IV and VI, suggesting NT4 protein production in thalamorecipient layers, but peak expression gradually shifted to upper layers as did NGF expression. The layer-specific developmental expression shifts of neurotrophin mRNAs correlate with morphogenetic processes.

Nerve growth factor is primarily produced by GABAergic neurons of the adult rat cortex

“…Previous studies have reported uneven distribution of NGF-labeled neurons in the cortical laminae (Pitts and Miller, 2000; Patz and Wahle, 2006). Quantitative analysis by layer was not performed in the current study, however, as NGF labeling intensity diminished with increasing distance from the colchicine injection site.…”

Experience‐dependent regulation of TrkB isoforms in rodent visual cortex

“…It is known that BDNF mRNA expression within primary visual cortex (V1) increases during development (Patz and Wahle, 2006), but while many experimenters examine V1 as a whole, rodent V1 can be broken down into two distinct regions. The monocular portion of V1 (mV1) contains neurons that are driven by only the contralateral eye, but binocular V1 (bV1) contains neurons that are driven by both eyes; thus the effects of visual deprivation in these two regions is not equivalent, and it is not known whether this generates differential regulation of BDNF expression.…”

Impaired transmission at corticothalamic excitatory inputs and intrathalamic GABAergic synapses in the ventrobasal thalamus of heterozygous BDNF knockout mice

“…Recently, a BDNF-dependent modulation of synaptic plasticity at excitatory glutamatergic inputs from the mammillary bodies into the anterior thalamus has been described (Tsanov et al, 2009). However, further BDNF-dependent mechanisms of synaptic modulation have not yet been investigated in the thalamic network, although layer V and VI pyramidal cells, which also project into the thalamus, strongly express BDNF in juvenile and adult rodents (Murer et al, 2001;Patz and Wahle, 2006), and BDNF is highly expressed in the VB of rats during postnatal (P3-P21) development (Mooney and Miller, 2011). Furthermore, TrkB receptor mRNA and TrkB receptor protein are clearly expressed in the ventrobasal thalamus of adult rats (Avwenagha et al, 2006).…”