Prenatal protein restriction alters synaptic mechanisms of callosal connections in the rat visual cortex

Abstract

Mild prenatal protein malnutrition, induced by reduction of the casein content of the maternal diet from 25 to 8%, calorically compensated by the addition of excess carbohydrates, leads to so-called ‘‘hidden’’ malnutrition in the rat. This form of malnutrition results in normal body and brain weights of pups at birth, but in significant alterations of their central nervous system neurochemical profiles. Since severe forms of prenatal malnutrition induce morpho-functional deficits on callosal interhemispheric communication together with brain neurochemical disturbances, we evaluated, in rats born from mothers submitted to an 8% casein diet, the potassium-induced release of [11Abbreviations : CC: corpus callosum ;[1H]-NA : tritiated noradrenaline ; KRB : Krebs–Ringer bicarbonate ; NA : noradrenaline ; TERs : transcallosal evoked responses.H]-noradrenaline in visual cortex slices, as well as functional properties of callosal-cortical synapses by determining cerebral cortical excitability to callosal inputs and fatigability and temporal summation of transcallosal evoked responses. Rats born from mothers submitted to a 25% casein diet served as controls. At birth prenatally malnourished pups had significantly higher cortical percent net noradrenaline release (14.79±1.11) than controls (9.14±1.26). At 45–50 days of age, rehabilitated previously malnourished rats showed, when compared to controls : (i) significantly reduced percent net noradrenaline release in the visual cortex (4.50±0.52 vs 11.31±1.14) ; (ii) decreased cortical excitability to callosal inputs as revealed by significantly increased chronaxie (607.2±82.8 μs vs 351.3±47.7 μs) ; (iii) enhanced fatigability of transcallosal evoked responses as revealed by significantly decreased stimulus frequency required to fatigate the responses (4.9±0.8 Hz vs 9.2±1.3 Hz) ; and (iv) decreased ability of callosal-cortical synapses to perform temporal summation, as revealed by significantly reduced percent response increment to double-shock (54.2±6.2 vs 83.0±11.0, for a 3.2-ms interstimulus time interval). These changes, resulting from mild prenatal protein restriction, are discussed in relationship to developmental processes leading to the formation of synaptic contacts between callosal axons and their appropriate cortical target during perinatal age.