Abstract
Protein malnutrition during early development has been correlated with cognitive and learning disabilities in children, but the neuronal deficits caused by long-term protein deficiency are not well understood. We exposed rats from gestation up to adulthood to a protein-deficient (PD) diet, to emulate chronic protein malnutrition in humans. The offspring exhibited significantly impaired performance on the ‘Gap-crossing’ (GC) task after reaching maturity, a behavior that has been shown to depend on normal functioning of the somatosensory cortex. The physiological state of the somatosensory cortex was examined to determine neuronal correlates of the deficits in behavior. Extracellular multi-unit recording from layer 4 (L4) neurons that receive direct thalamocortical inputs and layers 2/3 (L2/3) neurons that are dominated by intracortical connections in the whisker-barrel cortex of PD rats exhibited significantly low spontaneous activity and depressed responses to whisker stimulation. L4 neurons were more severely affected than L2/3 neurons. The response onset was significantly delayed in L4 cells. The peak response latency of L4 and L2/3 neurons was delayed significantly. In L2/3 and L4 of the barrel cortex there was a substantial increase in GAD65 (112% over controls) and much smaller increase in NMDAR1 (12-20%), suggesting enhanced inhibition in the PD cortex. These results show that chronic protein deficiency negatively affects both thalamo-cortical and cortico-cortical transmission during somatosensory information processing. The findings support the interpretation that sustained protein deficiency interferes with features of cortical sensory processing that are likely to underlie the cognitive impairments reported in humans who have suffered from prolonged protein deficiency.
Highlights
Protein deficiency in-utero and during early childhood has been correlated with detrimental effects on cognitive function [1,2,3,4,5] and on brain structures such as cerebral atrophy ventricular dilatation [6,7], myelination delay [8] and abnormal dendritic spines [9,10]
We examined sensory processing in the somatosensory whisker barrel cortex of PD rats to quantify deficits in (i) whiskerdependent somatosensory behavior; (ii) the response properties of cortical neurons that are driven by direct thalamic inputs; (iii) the response of neurons generated by intracortical connections and (iv) levels of excitation and inhibition in the somatosensory cortex
We examined the levels of glutamic acid decarboxylase 65 (GAD65) and N-methyl-D-aspartate receptor subunit1 (NMDAR1) in barrel cortex of PD and control rats
Summary
Protein deficiency in-utero and during early childhood has been correlated with detrimental effects on cognitive function [1,2,3,4,5] and on brain structures such as cerebral atrophy ventricular dilatation [6,7], myelination delay [8] and abnormal dendritic spines [9,10]. Animals exposed to PD diet during early development have cognitive and behavioral deficits [3], abnormalities in brain structures [16] including alterations in apical and basilar dendritic arborization and orientation of pyramidal cells in the neocortex [17,18,19], reduction in dendritic branching, number of spines, synapses and mossy fibre formation in hippocampus [20,21,22,23], malformation of hypothalamic nuclei [24] and anatomical changes in somatosensory cortex [25]. We tested the hypothesis that chronic exposure to protein deficiency from gestation to adulthood can impair sensory information processing and lead to behavioral deficits. Our results provide evidence that chronic protein deficiency leads to profound deficits in sensory processing and behavior
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
