Neonatal hippocampal lesions facilitate biconditional contextual discrimination learning in monkeys.

Abstract

This study examined whether selective neonatal hippocampal lesions in monkeys (Macaca mulatta), which left the surrounding cortical areas (parahippocampal cortex) intact, affect contextual learning and memory compared to controls. Monkeys were tested with an automated touch-screen apparatus so that stimuli and contextual cues could be manipulated independently of one another. The data suggest that animals with neonatal hippocampal lesions have sparing of function in regards to contextual learning and memory when (1) contextual information is irrelevant or (2) relevant for good discrimination performance, and (3) when transferring a contextual rule to new discriminations. These findings are at odds with studies examining contextual learning and memory in monkeys with selective adult-onset hippocampal lesions, and those with non-selective neonatal hippocampal lesions, which have demonstrated impairment in contextual learning and memory. Therefore, the sparing of function seen in this study may be due to the early nature of the damage and the plastic nature of the infant brain, as well as the intact medial temporal lobe cortical areas as a result of the lesion methodology. Specifically, by removing the hippocampus early in life, before it has begun to function, the parahippocampal (TH/TF) and perirhinal cortices and its interactions with the lateral prefrontal cortex may be able to support context processing throughout life.

Contributions of nonhuman primate research to understanding the consequences of human brain injury during development

“…49-51) documenting that, in adults, the declarative and procedural memory systems compete for cognitive control. Bachevalier's work (44,52) extends these findings to the developmental period.…”

Differential responses toward conditioned and unconditioned stimuli, but decreased hypothalamic-pituitary-adrenal axis responsiveness in neonatal hippocampal lesioned monkeys

“…Hippocampal lesions varied from 66% in one case to only 15% in another, with all other cases between 45% and 50% range. However, in all cases (even the smallest lesion) the damage included the anterior portion of the hippocampus (see ( Glavis-Bloom and Bachevalier, 2018 )). The anterior hippocampus has dense projections with the amygdala and ventromedial prefrontal cortex ( Aggleton, 1986 , Ongür and Price, 2000 , Alexander et al, 2019a , Alexander et al, 2019b ), two structures critical for emotional regulation (see review ( Aggleton, 2012 )).…”

Nonhuman primate models of hippocampal development and dysfunction

“…Similarly, rhesus monkeys with adultonset hippocampal lesions had greater difficulty recognizing an object when its background was different from that used during encoding (35). By contrast, adult monkeys with early-onset hippocampal lesions showed normal performance when they had to recognize an object when presented in a background different from the background used at encoding or when they had to learn biconditional discrimination problems (36). Thus, the sparing of contextual learning and memory likely resulted from the early onset of the hippocampal lesions that allowed for significant functional compensation by other brain structures playing an active role in processing contextual information, such as areas within the parahippocampal cortex (TH/TF) (34), the perirhinal cortex (35)(36)(37)(38)(39)(40)(41), and the prefrontal cortex (42,43).…”