Fig. 1: Proposed head direction cell circuit Fig. 2: Coronal section schematic of dorsal tegmental nucleus (DTN)

Fig.3: C-fos expression in the DTN in a trained rat

Pilot Study: Conditioning Rats to RotateKoula Quirk

RET Fellow 2009

RET Mentor: Dr. Dave Wirtshafter, Laboratory of Integrative Neuroscience Chicago Science Teacher Research Program (CSTR)NSF- RET Program

AbstractAbstractIntroductionIntroduction

ResultsResults

BackgroundBackground

Materials and MethodsMaterials and Methods

Future PlansFuture PlansFor their generosity and patient assistance I thank:

Dr. Dave Wirtshafter, Research Mentor, Laboratory of Integrative Neuroscience, UIC

Mary Clare Kane, PhD Candidate, UIC

Vishnu Mudrakola, Beth Cowgill, Research technicians, L.I.N, UIC

Prof. Andreas Linninger, RET Program Director

Sukhi Basati, LPPD, UIC

NSF CBET EEC-0743068 Grant

Acknowledgements

MotivationLevels of neurological disorders are rising and strike an Levels of neurological disorders are rising and strike an estimated 50 million Americans annuallyestimated 50 million Americans annually11 Implications for degenerative neurological conditions Implications for degenerative neurological conditions such as Parkinson’s and Alzheimer’s diseasesuch as Parkinson’s and Alzheimer’s disease

ObjectivesTo elucidate the neural pathway underlying the To elucidate the neural pathway underlying the navigational systemnavigational systemTo understand how the nervous system processes a To understand how the nervous system processes a high level cognitive signalhigh level cognitive signalPreliminary to future experiment to determine if trained Preliminary to future experiment to determine if trained rotation still occurs after lesioning rotation still occurs after lesioning

Source: National Institute of Neurological Disorders and StrokeSource: National Institute of Neurological Disorders and Stroke11

SubjectsThree adult male Sprague-Dawley rats (Charles River Lab. Int., Inc.) weighing 300 to 350g originally, deprived to 85% at the start of training were used. They had ad lib access to water and were individually housed in acrylic shoebox cages under a 12:12 light-dark cycle.

ApparatusThe operant chamber was 22x23cm with 2 metal opposing walls and 2 clear acrylic walls. A small side box, 5x5cm, extended out from one of the metal walls. This allowed the lever to introduce the reward. The floor consisted of a metal rod grid allowing fecal matter to drop to the tray bedding below. The reward was a 1:1 dilution of sweetened condensed milk/de-ionized water.

The navigational signal is thought to originate in the dorsal tegmental nucleus (DTN) within the proposed head direction cell circuit (Fig.1). The DTN (Fig. 2) is activated contralaterally to head turning. The neurons in the rat limbic system discharge depending on the rat’s directional heading in space. C-fos is a gene whose expression can be used to map out activated pathways in the brain. We study this circuit by examining c-fos expression in rats trained to rotate (Fig. 3). We wish to examine if, after unilateral lesioning of the DTN, the rats will still be able to rotate as they were previously trained.

Training took place in a low light/low noise enclosed room. The operant chamber was connected to a remote cable with an attached push button. When the rat rotated correctly, the researcher pressed the button raising the food hopper containing 50l of milk. Each rat had 45minutes of training daily for 3 weeks. One rat was trained to rotate clockwise the others counterclockwise. Rats were fed 13g of LabDiet food 10min post training. All experiments conformed to the NIH Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee.

AlphaR feeding

Methods

The experiment has not concluded. The three rats have been successfully trained to rotate: one clockwise, the other two in a counterclockwise direction.

Bilaterally lesion the section of the brain (dorsal tegmental nucleus)

Determine if trained rats can still rotate after lesioning

Section the rat brain to locate c-fos expression in the DTN