Physiological Slowing and Upregulation of Inhibition in Cortex Are Correlated with Behavioral Deficits in Protein Malnourished Rats

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.

Low protein diet during gestation and lactation increases food reward seeking but does not modify sucrose taste reactivity in adult female rats

“…Numerous studies have attempted to elucidate the impact of the insults occurring in development and early life (Chaudhary et al, 2013; da Silva et al, 2013; Dyer and Rosenfeld, 2011). In this sense, there is thought to be a strong relationship between an inadequate diet, imbalanced neurotransmission, and important neurological disorders (Chaudhary et al, 2013). The results of the present investigation demonstrate that exposure to low protein diet during gestation and lactation can affect feeding behaviours in adult female rats.…”

“…Numerous studies have attempted to elucidate the impact of the insults occurring in development and early life (Chaudhary et al, 2013;Dyer and Rosenfeld, 2011). In this sense, there is thought to be a strong relationship between an inadequate diet, imbalanced neurotransmission, and important neurological disorders (Chaudhary et al, 2013).…”

Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children

“…In the absence of infection, protein-energy malnutrition has an adverse effect on behavior compared with nutrient sufficiency in rats. 114,115 Additional studies show that behaviors of undernourished dams and their offspring are negatively impacted, 115,116 linking diet and microbiota (by proxy) to brain function. Metabolism of food by the host (and perhaps by the mother) has the potential to affect host genetics.…”

Effects of perinatal undernutrition on social transmission of food preference in adult male Wistar rats

“…In addition to possible deleterious health consequences, early malnutrition or undernutrition is known to cause impaired cognitive functions in infants, with long‐term effects in adulthood (Al‐Harbi et al, 2017; Pérez‐García et al, 2016; Peter et al, 2016). Studies in both rodents and humans have demonstrated that several cognitive deficits are produced by perinatal food restriction, including deficient attentional performance, emotional reactivity, and short and long‐term memory processes (Chaudhary et al, 2013; McGaughy et al, 2014; Rotta et al, 2008). Undernutrition also plays a critical role in the consolidation of certain types of memories, although the brain mechanisms involved are not fully understood.…”