The Neonatal Ventral Hippocampal Lesion (NVHL) Rodent Model of Schizophrenia

Anne Marie Brady1

1 Department of Psychology and Neuroscience Program, St. Mary's College of Maryland, St. Mary's City, Maryland
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.55
DOI:  10.1002/cpns.15
Online Posting Date:  October, 2016
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Abstract

Animal models are crucial to the study of the neurobiological bases of psychiatric disorders, but schizophrenia is a particularly challenging disorder to model given the complexity and heavily verbal nature of its symptoms. This unit describes a developmental surgical rodent model of schizophrenia, the neonatal ventral hippocampal lesion (NVHL) model. This widely used model produces reliable behavioral abnormalities that are comparable to those observed in patients, as well as anatomical and neurophysiological disruptions in forebrain areas that are also implicated in schizophrenia. A brief background of the development and validity of the NVHL model is discussed here, along with detailed procedures for producing the model in rats. Critical issues particular to neonatal surgery are discussed, and representative histological and behavioral results are presented. © 2016 by John Wiley & Sons, Inc.

Keywords: developmental; hippocampus; prefrontal cortex; rodent model; schizophrenia

     
 
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Table of Contents

  • Introduction
  • Basic Protocol 1: Presurgical Preparation of Animals
  • Basic Protocol 2: The NVHL Surgical Procedure
  • Support Protocol 1: Preparation of the Stereotaxic Frame and Injection Cannula
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
     
 
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Materials

Basic Protocol 1: Presurgical Preparation of Animals

  Materials
  • Pregnant Sprague Dawley rats
  • Rodent housing facility
  • Scale, to weigh pups
  • Additional reagents and equipment for euthanasia ( appendix 4H)

Basic Protocol 2: The NVHL Surgical Procedure

  Materials
  • Rat dams and litters (PD 7 ± 1)
  • Artificial cerebrospinal fluid (aCSF; see recipe)
  • 10 µg/µl ibotenic acid (see recipe)
  • Scale, to weigh pups
  • Polyethylene (PE‐20) tubing (i.d. 0.38 to 0.4 mm, o.d. 1.09 to 1.1 mm)
  • Injection cannula assembly (26‐G needle with sharp bevel [e.g., Hamilton 775802] and depth marker [see protocol 3Support Protocol])
  • 1‐ml syringes with 23‐G or 25‐G needles
  • 10‐μl infusion syringe (e.g., Hamilton 80300)
  • Syringe infusion pump capable of delivering 15 nl/min
  • Crushed ice and ice bucket
  • Stereotaxic frame, modified (see protocol 3Support Protocol)
  • Self‐adhesive label tape
  • Scalpel blades
  • Ear punch or tattooing equipment
  • Clip applier and clips (e.g., Autoclip System) or wound closure glue
  • Toothed iris tissue forceps (1 × 2 teeth, straight, 4 in.)
  • Rubber pipet bulbs
  • Warming pads (e.g., Deltaphase 8 in. × 8 in. pads)
  • Alcohol (for sterilizing instruments) or heat‐based instrument sterilizer (e.g., Germinator 500)

Support Protocol 1: Preparation of the Stereotaxic Frame and Injection Cannula

  Materials
  • Section of thick Styrofoam or similar material, sized to fit inside the stereotaxic frame
  • Small animal stereotaxic frame with ear bars (e.g., Kopf Model 900)
  • Standard vertical electrode holder with clamp (e.g., Kopf Model 1770)
  • Circular (bulls‐eye) level (allows leveling in two dimensions)
  • Polyethylene (PE‐20) tubing (i.d. 0.38 to 0.4 mm, o.d. 1.09 to 1.1 mm)
  • Injection cannula (26‐G needle with sharp bevel [e.g., Hamilton 775802])
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Figures

Videos

Literature Cited

Literature Cited
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