Related Experiment Video
Updated: Aug 25, 2026
Preparation of Acute Slices from Dorsal Hippocampus for Whole-Cell Recording and Neuronal Reconstruction in the Dentate Gyrus of Adult Mice
Published on: April 3, 2021
Method for making selective lesions of the hippocampus in macaque monkeys using NMDA and a longitudinal surgical
Robert R Hampton1, Cindy A Buckmaster, Dawn Anuszkiewicz-Lundgren
1Section on the Neurobiology of Learning and Memory, Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. robert@ln.nimh.nih.gov
Abstract:
We describe a method for making selective lesions of the hippocampus in macaque monkeys, using a magnetic resonance imaging (MRI)-guided stereotaxic approach in which the excitotoxin N-methyl-D-aspartic acid (NMDA) is injected at intervals along a single needle track that extends longitudinally through the rostrocaudal extent of the hippocampus. Procedures were conducted on six rhesus monkeys (Macaca mulatta) and were assessed with either in vivo MRI (n = 3) or postmortem microscopic examination of the tissue after standard histological processing of the brains (n = 3). Based on our extensive experience with the standard stereotaxic procedure in which ibotenic acid (IBO) is injected via the dorsal approach, we report that the new method provides a viable and potentially advantageous alternative to the standard procedure. First, the longitudinal approach combined with N-methyl-D-aspartic acid (NMDA) injections increases the reliability and efficacy of hippocampal excitotoxic lesions, probably by limiting the leakage of injectant into the ventricles. Second, the present procedure led to more rapid postoperative recovery compared with that after the standard procedure. Third, because the new method requires fewer needle penetrations than the standard method, it most likely reduces the chances of infarction in extrahippocampal tissue. Finally, the new surgical approach may provide a mechanism for infusing agents into the hippocampus from a single cannula.
Insights
This study introduces a new MRI-guided method for creating precise hippocampal lesions in monkeys using N-methyl-D-aspartic acid (NMDA). This technique offers improved reliability, faster recovery, and reduced tissue damage compared to standard methods.
Area of Science:
- Neuroscience
- Primate Research
- Surgical Techniques
Background:
- Selective hippocampal lesions are crucial for studying memory and cognition in non-human primates.
- Standard stereotaxic methods using ibotenic acid (IBO) have limitations, including potential off-target effects and slower recovery.
Purpose of the Study:
- To describe and evaluate a novel magnetic resonance imaging (MRI)-guided stereotaxic approach for creating selective hippocampal lesions in macaque monkeys.
- To compare the efficacy, safety, and recovery profile of this new method with the standard ibotenic acid (IBO) dorsal approach.
Main Methods:
- A longitudinal stereotaxic technique was employed in six rhesus monkeys (Macaca mulatta).
- Excitotoxic N-methyl-D-aspartic acid (NMDA) was injected along a single needle track through the hippocampus.
- Lesions were assessed using in vivo MRI or postmortem histological analysis.
Main Results:
- The NMDA longitudinal approach demonstrated increased reliability and efficacy in lesion creation, likely due to reduced ventricular leakage.
- Monkeys exhibited more rapid postoperative recovery compared to the standard IBO procedure.
- Fewer needle penetrations minimized the risk of extrahippocampal infarction.
Conclusions:
- The described MRI-guided longitudinal NMDA injection method is a viable and advantageous alternative for creating selective hippocampal lesions in macaque monkeys.
- This technique offers enhanced precision, improved recovery, and reduced collateral damage.
- The approach may also facilitate single-cannula infusion of agents into the hippocampus.
