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Transneuronal regulation of tyrosine hydroxylase expression in olfactory bulb of mouse and rat
Abstract:
Peripheral afferent input regulates the expression of dopaminergic properties in a population of local circuit intrinsic neurons of the rodent olfactory bulb. Lesions of the olfactory receptor neurons produced in the mouse by intranasal irrigation with either ZnSO4 or Triton X-100 and in the rat by surgical deafferentation or axotomy are associated with a decrease in the levels of dopamine (DA), the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), the activity of the enzyme tyrosine hydroxylase (TH), bulb weight and an increase in norepinephrine (NE) levels in the olfactory bulb. The anatomical correlates of the biochemical sequelae of deafferentation of olfactory bulb DA neurons were studied using immunohistochemical techniques to localize TH. Within 3 to 4 weeks all lesions produced a dramatic and uniform reduction in TH staining of the juxtaglomerular DA neurons and their processes which was paralleled by a reduction in DA and DOPAC levels and bulb weight. Seven weeks following reversible chemical lesions produced by Triton X-100, DA and DOPAC levels and tissue weight as well as TH staining in the juxtaglomerular neurons returned to control levels. These observations suggested that DA neurons remained present even when not demonstrable with TH antibodies. Additional evidence for the continued presence of the DA neurons was the ability of the olfactory bulbs from both lesioned mouse and rat to synthesize DA from exogenously administered L-3,4-dihydroxyphenylalanine (l-DOPA). These data suggested that the decrease in DA levels and TH staining in the olfactory bulb following lesions of the olfactory receptor neurons were produced by transneuronal mechanisms since there was no direct injury of the bulb. Furthermore, the demonstration that following reinnervation, catecholamine synthetic capacity is restored suggests that the juxtaglomerular dopamine neurons remain in the bulb and that afferent receptor input is required for expression of TH enzyme.
Insights
Peripheral afferent input regulates dopamine expression in the olfactory bulb. Receptor neuron lesions decrease dopamine and tyrosine hydroxylase, but neurons persist and recover function after reinnervation.
Area of Science:
- Neuroscience
- Olfactory System Research
- Neurochemistry
Background:
- The olfactory bulb's dopaminergic neurons are intrinsic local circuit neurons.
- Peripheral afferent input influences the expression of dopaminergic properties in these neurons.
Purpose of the Study:
- To investigate the impact of olfactory receptor neuron lesions on dopaminergic neurons in the rodent olfactory bulb.
- To understand the mechanisms regulating dopamine and tyrosine hydroxylase expression in these neurons.
Main Methods:
- Olfactory receptor neuron lesions induced using ZnSO4, Triton X-100, or surgical deafferentation in mice and rats.
- Biochemical analysis of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and norepinephrine (NE) levels.
- Immunohistochemical localization of tyrosine hydroxylase (TH) to assess dopaminergic neuron integrity.
- Assessment of olfactory bulb weight.
- In vitro synthesis of DA from L-3,4-dihydroxyphenylalanine (l-DOPA) in lesioned olfactory bulbs.
Main Results:
- Lesions led to decreased DA, DOPAC, TH activity, and olfactory bulb weight, with increased NE levels.
- TH staining in juxtaglomerular dopaminergic neurons and their processes significantly reduced within 3-4 weeks post-lesion.
- Reversible lesions showed recovery of DA, DOPAC, bulb weight, and TH staining within 7 weeks.
- Lesioned olfactory bulbs retained the capacity to synthesize DA from l-DOPA, indicating neuron survival.
Conclusions:
- Olfactory receptor neuron deafferentation causes transneuronal downregulation of dopamine and TH expression in olfactory bulb neurons.
- The juxtaglomerular dopaminergic neurons survive deafferentation and can recover catecholamine synthetic capacity upon reinnervation.
- Afferent input from olfactory receptor neurons is crucial for maintaining tyrosine hydroxylase expression in these intrinsic neurons.