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The role of the hippocampus in avoidance learning and anxiety vulnerability.

Cominski TP, Jiao X, Catuzzi JE, Stewart AL, Pang KC - Front Behav Neurosci (2014)

Bottom Line: In the current study, we examined the effect of hippocampal damage in avoidance learning, as avoidance is a core symptom of all anxiety disorders.The WKY rat is an animal model of behavioral inhibition, a risk factor for anxiety, and demonstrates abnormal avoidance learning, marked by facilitated avoidance acquisition and resistance to extinction.These results suggest that hippocampal dysfunction enhances the development of persistent avoidance responding and, thus, may confer vulnerability to the development of anxiety disorders and PTSD.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neurosciences, Rutgers - New Jersey Medical School, Rutgers, The State University of New Jersey , Newark, NJ , USA.

ABSTRACT
The hippocampus has been implicated in anxiety disorders and post-traumatic stress disorder (PTSD); human studies suggest that a dysfunctional hippocampus may be a vulnerability factor for the development of PTSD. In the current study, we examined the effect of hippocampal damage in avoidance learning, as avoidance is a core symptom of all anxiety disorders. First, the effect of hippocampal damage on avoidance learning was investigated in outbred Sprague Dawley (SD) rats. Second, the function of the hippocampus in Wistar-Kyoto (WKY) rats was compared to SD rats. The WKY rat is an animal model of behavioral inhibition, a risk factor for anxiety, and demonstrates abnormal avoidance learning, marked by facilitated avoidance acquisition and resistance to extinction. The results of the current study indicate that hippocampal damage in SD rats leads to impaired extinction of avoidance learning similar to WKY rats. Furthermore, WKY rats have reduced hippocampal volume and impaired hippocampal synaptic plasticity as compared to SD rats. These results suggest that hippocampal dysfunction enhances the development of persistent avoidance responding and, thus, may confer vulnerability to the development of anxiety disorders and PTSD.

No MeSH data available.


Related in: MedlinePlus

Excitotoxic lesions of the hippocampus and entorhinal cortex. The black shaded regions indicate the smallest lesion observed and gray shaded regions indicate the largest lesion observed. (A–C) depict the hippocampal lesion at three different anterior–posterior locations (approximately -2.76, -4.80, and -6.36 mm from bregma). (D–F) represent the entorhinal cortex lesion at three different anterior–posterior sites (approximately -6.36, -7.20, and -7.68 mm from bregma).
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Figure 1: Excitotoxic lesions of the hippocampus and entorhinal cortex. The black shaded regions indicate the smallest lesion observed and gray shaded regions indicate the largest lesion observed. (A–C) depict the hippocampal lesion at three different anterior–posterior locations (approximately -2.76, -4.80, and -6.36 mm from bregma). (D–F) represent the entorhinal cortex lesion at three different anterior–posterior sites (approximately -6.36, -7.20, and -7.68 mm from bregma).

Mentions: Rats were anesthetized with isoflurane (2%). Burr holes were drilled into the skull overlying the hippocampus or entorhinal cortex. The coordinates (in mm) for the entorhinal cortex lesion sites in relation to bregma were as follows (four sites per hemisphere): AP -5.3, ML ±6.5, DV -5.0; AP -6.0, ML ±6.5, DV -5.0; AP -6.7, ML ±5.0, DV -6.5; AP -7.4, ML ± 5.0, DV -6.5. The coordinates for the hippocampal lesion sites in relation to bregma were as follows (five sites per hemisphere): AP -2.5, ML ±1.6, DV -3.8; AP -4.2, ML ±2.6, DV -3.1; AP -5.3, ML ±4.4, DV -3.4; AP -5.8, ML ±5.6, DV -4.1; AP -6.0, ML ±5.6, DV -4.1. Injections were made bilaterally. The needle of a Hamilton syringe was inserted into the desired location to infuse saline for sham surgery or ibotenic acid (10 μg/μl) to damage hippocampus or entorhinal cortex. Infusions occurred at a rate of 0.1 μl/min with a volume of 0.5 μl dispensed per site. Rats were allowed at least 10 days to recover from surgery. Extent and location of lesions are depicted in Figure 1.


The role of the hippocampus in avoidance learning and anxiety vulnerability.

Cominski TP, Jiao X, Catuzzi JE, Stewart AL, Pang KC - Front Behav Neurosci (2014)

Excitotoxic lesions of the hippocampus and entorhinal cortex. The black shaded regions indicate the smallest lesion observed and gray shaded regions indicate the largest lesion observed. (A–C) depict the hippocampal lesion at three different anterior–posterior locations (approximately -2.76, -4.80, and -6.36 mm from bregma). (D–F) represent the entorhinal cortex lesion at three different anterior–posterior sites (approximately -6.36, -7.20, and -7.68 mm from bregma).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125878&req=5

Figure 1: Excitotoxic lesions of the hippocampus and entorhinal cortex. The black shaded regions indicate the smallest lesion observed and gray shaded regions indicate the largest lesion observed. (A–C) depict the hippocampal lesion at three different anterior–posterior locations (approximately -2.76, -4.80, and -6.36 mm from bregma). (D–F) represent the entorhinal cortex lesion at three different anterior–posterior sites (approximately -6.36, -7.20, and -7.68 mm from bregma).
Mentions: Rats were anesthetized with isoflurane (2%). Burr holes were drilled into the skull overlying the hippocampus or entorhinal cortex. The coordinates (in mm) for the entorhinal cortex lesion sites in relation to bregma were as follows (four sites per hemisphere): AP -5.3, ML ±6.5, DV -5.0; AP -6.0, ML ±6.5, DV -5.0; AP -6.7, ML ±5.0, DV -6.5; AP -7.4, ML ± 5.0, DV -6.5. The coordinates for the hippocampal lesion sites in relation to bregma were as follows (five sites per hemisphere): AP -2.5, ML ±1.6, DV -3.8; AP -4.2, ML ±2.6, DV -3.1; AP -5.3, ML ±4.4, DV -3.4; AP -5.8, ML ±5.6, DV -4.1; AP -6.0, ML ±5.6, DV -4.1. Injections were made bilaterally. The needle of a Hamilton syringe was inserted into the desired location to infuse saline for sham surgery or ibotenic acid (10 μg/μl) to damage hippocampus or entorhinal cortex. Infusions occurred at a rate of 0.1 μl/min with a volume of 0.5 μl dispensed per site. Rats were allowed at least 10 days to recover from surgery. Extent and location of lesions are depicted in Figure 1.

Bottom Line: In the current study, we examined the effect of hippocampal damage in avoidance learning, as avoidance is a core symptom of all anxiety disorders.The WKY rat is an animal model of behavioral inhibition, a risk factor for anxiety, and demonstrates abnormal avoidance learning, marked by facilitated avoidance acquisition and resistance to extinction.These results suggest that hippocampal dysfunction enhances the development of persistent avoidance responding and, thus, may confer vulnerability to the development of anxiety disorders and PTSD.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neurosciences, Rutgers - New Jersey Medical School, Rutgers, The State University of New Jersey , Newark, NJ , USA.

ABSTRACT
The hippocampus has been implicated in anxiety disorders and post-traumatic stress disorder (PTSD); human studies suggest that a dysfunctional hippocampus may be a vulnerability factor for the development of PTSD. In the current study, we examined the effect of hippocampal damage in avoidance learning, as avoidance is a core symptom of all anxiety disorders. First, the effect of hippocampal damage on avoidance learning was investigated in outbred Sprague Dawley (SD) rats. Second, the function of the hippocampus in Wistar-Kyoto (WKY) rats was compared to SD rats. The WKY rat is an animal model of behavioral inhibition, a risk factor for anxiety, and demonstrates abnormal avoidance learning, marked by facilitated avoidance acquisition and resistance to extinction. The results of the current study indicate that hippocampal damage in SD rats leads to impaired extinction of avoidance learning similar to WKY rats. Furthermore, WKY rats have reduced hippocampal volume and impaired hippocampal synaptic plasticity as compared to SD rats. These results suggest that hippocampal dysfunction enhances the development of persistent avoidance responding and, thus, may confer vulnerability to the development of anxiety disorders and PTSD.

No MeSH data available.


Related in: MedlinePlus