Name: new variations for strategy set-shifting in the rat
Uploaded: 2017-01-23T13:00:00
Description: Watch this Scientific Journal Video about New Variations for Strategy Set-shifting in the Rat at JoVE.com

This study was supported by Human Frontier Science Program and the Sasakawa Scientific Research Grant from the Japan Science Society.

All procedures for the use of animals were approved by the Animal Care and Use Committee at the Okinawa Institute of Science and Technology.
1. Animals
<ol>
	<li>Obtain male Long-Evans rats (250-300 g on arrival).</li>
	<li>Upon arrival, house a group of two or three rats together for a week and later separate them into individual cages. Note that this experimental design involves food-restriction and needs to hold an animal in each cage to control the amount food consumed.</li>
	<li>Provide...

<ol>
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We developed new variations on the established set-shifting paradigm for use in rats. Using those paradigms, cholinergic lesions of the striatum were found to impair set-shifting, suggesting a specific role of striatal cholinergic interneurons in set-shifting: suppression of an old rule and facilitation of exploration for a new rule. The effects differed between dorsomedial and ventral striatum, in accordance with the different role of these structures in learning.
A set-shifting task has been...

Behavioral flexibility is a key requirement for survival in a changing world. One of the established behavioral paradigms for testing this ability is set-shifting, in which a shift of attention from one stimulus dimension to another is necessary for changing action strategies after a change in rule. Several brain regions such as the prefrontal cortex and striatum are implicated in set-shifting2,3,4,5. Neural mechanisms for this function have been investigated across several species including humans5, monkeys6 and rats1,7,8,9. However, the rat versions of set-shifting tasks have not been as extensively developed. The cost-effectiveness of rats, their appropriate size for stereotaxic surgery, and the availability of recently developed genetic methods10, motivate further development of set-shifting paradigms for use in rats.
A typical set-shifting paradigm for rats requires a change between two behavioral strategies: for example, a response strategy and a visual-cue strategy. Rats initially have to choose one of two available options (such as left or right levers in an operant automated version1 or left or right arms in a T-maze version7,8,9,11). After a set shift, they have to switch to using a visual-cue strategy, such as a light cue indicating the correct side. In those conventional set-shifting tasks, it is necessary to shift attention from one stimulus dimension to another dimension that had been previously irrelevant.
In addition to changing to a dimension that had been previously irrelevant, there is also the logical possibility that a stimulus was previously relevant, or previously absent and now novel. Real life situations in nature may entail attention to a novel, or historically relevant but not crucial cue. Therefore, we considered these subtypes of set-shift, in a new variation of rodent set-shifting based on a previously established automated set-shifting task1.
We have recently demonstrated the use of the new version of set-shifting paradigms in an experiment to determine the effect of neurochemically specific lesions of the striatum12. In our previous study, we targeted cholinergic interneurons releasing acetylcholine (ACh) of the dorsomedial or ventral striatum since ACh and those subregions have been implicated in behavioral flexibility. All the experimental conditions demanded the same strategic shift but each involved different types of attentional shift: to a novel, previously relevant or previously irrelevant cue. We here describe detailed procedures of the paradigms, and highlight representative results suggesting that striatal cholinergic systems play a fundamental role in set-shifting, which is dissociable between different striatal subregions depending on behavioral contexts12.

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			<td height="21" style="height:21px;width:283px;">Standard Modular Test Chamber</td>
			<td style="width:97px;">Med Associates</td>
			<td style="width:119px;">ENV-008</td>
			<td style="width:189px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Low Profile Retractable Response Lever</td>
			<td>Med Associates</td>
			<td>ENV-112CM</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Stimulus Light for Rat</td>
			<td>Med Associates</td>
			<td>ENV-221M</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Switchable Dual Pellet/Dipper Receptacle for Rat</td>
			<td>Med Associates</td>
			<td>ENV-202RM-S</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Head Entry Detector for Rat Receptacles</td>
			<td>Med Associates</td>
			<td>ENV-254-CB</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Modular Pellet Dispenser; 45 mg for Rat</td>
			<td>Med Associates</td>
			<td>ENV-203M-45</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Sonalert Module for Rat</td>
			<td>Med Associates</td>
			<td>ENV-223AM</td>
			<td>4.5 kHz available (ENV-223HAM)</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">House Light for Rat Chambers</td>
			<td>Med Associates</td>
			<td>ENV-215M</td>
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		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">SmartCtrl Interface Module, 8 input/16 output</td>
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			<td>DIG-716B</td>
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		<tr height="21">
			<td height="21" style="height:21px;">SmartCtrl Connection Panel, 8 input/16 output</td>
			<td>Med Associates</td>
			<td>SG-716B</td>
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			<td height="21" style="height:21px;">45 mg Tablet-Fruit Punch</td>
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new variations for strategy set-shifting in the rat

Behavioral flexibility is crucial for survival in changing environments. Broadly defined, behavioral flexibility requires a shift of behavioral strategy based on a change in governing rules. We describe a strategy set-shifting task that requires an attentional shift from one stimulus dimension to another. The paradigm is often used for testing cognitive flexibility in primates. However, the rodent version has not been as extensively developed. We have recently extended an established set-shifting task in the rat1 by requiring attention to different stimuli according to context. All the experimental conditions required animals to choose either a left or right lever. Initially, all animals had to choose on the basis of the location of the lever. Subsequently, a change in the rule occurred, which required a shift in set from location-based rule to a rule in which the correct lever was indicated by a light cue. We compared performance on three different versions of the task, in which the light stimulus was either novel, previously relevant, or previously irrelevant. We found that specific neurochemical lesions selectively impaired the ability to make particular types of set shift as measured by the performance on the different versions of the task.

We used the strategy set-shifting task described above to investigate the role of cholinergic interneurons in behavioral flexibility. We compared the effect on the task of an immunotoxin-induced selective lesion of cholinergic interneurons in dorsomedial (DMS), ventral striatum (VS) and saline-injected control. All animals had to switch from choosing a lever based on the side (left or right), to choosing based on a cue light above the correct lever. We used three experimental conditions of set-shift in which the cue ligh...

Watch this Scientific Journal Video about New Variations for Strategy Set-shifting in the Rat at JoVE.com

New Variations for Strategy Set-shifting in the Rat

Set-shifting, a form of behavioral flexibility, requires an attentional shift from one stimulus dimension to another. We extended an established rodent set-shifting task1 by requiring attention to different stimuli according to context. The task was combined with specific lesions to identify neuron subtypes underlying a successful shift.

Behavioral flexibility is crucial for survival in changing environments. Broadly defined, behavioral flexibility requires a shift of behavioral strategy ...

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