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Multiple neuromodulator depletion interacts with fornix transection to impair episodic memory in monkeys.

Croxson PL, Baxter MG (2009) Multiple neuromodulator depletion interacts with fornix transection to impair episodic memory in monkeys. Neuroscience 2009 Abstracts 98.4/EE128. Society for Neuroscience, Chicago, IL.

Summary: Acetylcholine may play an important role in some aspects of cognitive function, and in particular in episodic memory. However, the role of other neuromodulatory (NM) substances, such as noradrenaline, dopamine, and serotonin, in episodic memory is less well-defined. We tested monkeys on a model of episodic memory in monkeys and carried out specific depletions of different neuromodulators within inferotemporal cortex (IT). Six rhesus macaque monkeys (five male) were trained on an object-in-place scene learning task that models key features of human episodic memory, because learning occurs rapidly (often in a single trial) in the contaxt of unique background scenes. After preoperative testing three monkeys were given injections into IT of the immunotoxin ME20.4-saporin interleaved with injections of 6-hydroxydopamine and 5,7-dihydroxytryptamine. This resulted in depletion of acetylcholine, dopamine, noradrenaline and serotonin throughout IT (group NM+ACh). Three monkeys received the same treatment but omitting the ME20.4-saporin, thus depleting dopamine, noradrenaline and serotonin, but sparing acetylcholine (group NM). Neither group of monkeys (NM+ACh or NM) were impaired in postoperative scene learning. We found previously that addition of fornix transection to depletion of ACh from IT severely impaired scene learning relative to fornix transection alone (Browning et al. 2009, Cerebral Cortex). Therefore we gave each monkey in groups NM and NM+ACh a bilateral fornix transection and performed a further postoperative performance test. As expected, monkeys in group NM+ACh were severely impaired in scene learning following fornix transection. However, monkeys in group NM were also severely impaired in scene learning following fornix transection, despite having no visible damage to cholinergic innervation. Depletion of cholinergic, dopaminergic, adrenergic and serotoninergic innervation of inferotemporal cortex, therefore, is not sufficient to impair monkeys’ performance on an episodic memory task. Furthermore, there is a synergistic interaction between the NM depletion and fornix transection in this task, like that between ACh depletion and fornix transection. This may be due to a general reduction in cortical function after NM depletion, albeit not sufficient to cause episodic memory impairment on its own, which exacerbates the effect of fornix transection. It may point to one or more of these neuromodulators having a role in post-lesion plasticity, a role that is also played by ACh. Importantly, these data suggest that intact cholinergic innervation is not sufficient for post-lesion plasticity.

Related Products: ME20.4-SAP (Cat. #IT-15)