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Altered Neuronal Dynamics in the Striatum on the Behavior of Huntingtin Interacting Protein 14 (HIP14) Knockout Mice.

Estrada-Sánchez AM, Barton SJ, Rebec GV - Brain Sci (2013)

Bottom Line: Striatal LFP activity anticipates this difference.In wild-types, the power spectral density pattern associated with entry into the choice point differs significantly from the pattern immediately before entry, especially at low frequencies (≤13 Hz), whereas HIP14 knockouts show no change in LFP activity as they enter the choice point.Our results suggest that HIP14 plays a critical role in the aberrant behavioral modulation of striatal neuronal activity underlying motor inflexibility, including the motor signs of HD.

View Article: PubMed Central - PubMed

Affiliation: Program in Neuroscience, Indiana University, Bloomington, IN 47405, USA.

ABSTRACT
Huntington's disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, impairs information processing in the striatum, which, as part of the basal ganglia, modulates motor output. Growing evidence suggests that huntingtin interacting protein 14 (HIP14) contributes to HD neuropathology. Here, we recorded local field potentials (LFPs) in the striatum as HIP14 knockout mice and wild-type controls freely navigated a plus-shaped maze. Upon entering the choice point of the maze, HIP14 knockouts tend to continue in a straight line, turning left or right significantly less often than wild-types, a sign of motor inflexibility that also occurs in HD mice. Striatal LFP activity anticipates this difference. In wild-types, the power spectral density pattern associated with entry into the choice point differs significantly from the pattern immediately before entry, especially at low frequencies (≤13 Hz), whereas HIP14 knockouts show no change in LFP activity as they enter the choice point. The lack of change in striatal activity may explain the turning deficit in the plus maze. Our results suggest that HIP14 plays a critical role in the aberrant behavioral modulation of striatal neuronal activity underlying motor inflexibility, including the motor signs of HD.

No MeSH data available.


Related in: MedlinePlus

HIP14 knockouts (HIP14 KO) are less likely to turn left or right as they explore the plus-shaped maze. The graph shows the turning probability obtained after wild-type and HIP14 knockout mice freely explored the plus maze for 30 min. The probability was obtained from the sum of arm choices to the right or left arm divided by the total number of arm choices. Wild-type and HIP14 knockout mice participated in multiple sessions for a total of 38 and 46 sessions, respectively. Data were analyzed by the unpaired t-test. Data are expressed as the mean ± SEM. t = 3.6; df = 82; * p = 0.0001.
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brainsci-03-01588-f001: HIP14 knockouts (HIP14 KO) are less likely to turn left or right as they explore the plus-shaped maze. The graph shows the turning probability obtained after wild-type and HIP14 knockout mice freely explored the plus maze for 30 min. The probability was obtained from the sum of arm choices to the right or left arm divided by the total number of arm choices. Wild-type and HIP14 knockout mice participated in multiple sessions for a total of 38 and 46 sessions, respectively. Data were analyzed by the unpaired t-test. Data are expressed as the mean ± SEM. t = 3.6; df = 82; * p = 0.0001.

Mentions: When mice enter the center or choice point of the plus maze, they have the option of continuing straight into the opposite arm or turning into either the left or right arm [11]. Wild-type (n = 10) and HIP14 knockout mice (n = 10) participated in multiple recording sessions; each mouse participated in at least two sessions for a total of 38 and 46 sessions, respectively, for each group. As Figure 1 shows, wild-type mice turn to explore the perpendicular arms with a probability of 0.71 ± 0.01. In contrast, HIP14 knockout mice are less likely to turn (the probability of turning is 0.60 ± 0.02); instead, once they cross the choice point, they explore the opposite arm. Statistical analysis of the probability of turning revealed a significant difference between wild-type and HIP14 knockout mice (t = 3.6, degrees of freedom (df) = 82, p = 0.0005).


Altered Neuronal Dynamics in the Striatum on the Behavior of Huntingtin Interacting Protein 14 (HIP14) Knockout Mice.

Estrada-Sánchez AM, Barton SJ, Rebec GV - Brain Sci (2013)

HIP14 knockouts (HIP14 KO) are less likely to turn left or right as they explore the plus-shaped maze. The graph shows the turning probability obtained after wild-type and HIP14 knockout mice freely explored the plus maze for 30 min. The probability was obtained from the sum of arm choices to the right or left arm divided by the total number of arm choices. Wild-type and HIP14 knockout mice participated in multiple sessions for a total of 38 and 46 sessions, respectively. Data were analyzed by the unpaired t-test. Data are expressed as the mean ± SEM. t = 3.6; df = 82; * p = 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061888&req=5

brainsci-03-01588-f001: HIP14 knockouts (HIP14 KO) are less likely to turn left or right as they explore the plus-shaped maze. The graph shows the turning probability obtained after wild-type and HIP14 knockout mice freely explored the plus maze for 30 min. The probability was obtained from the sum of arm choices to the right or left arm divided by the total number of arm choices. Wild-type and HIP14 knockout mice participated in multiple sessions for a total of 38 and 46 sessions, respectively. Data were analyzed by the unpaired t-test. Data are expressed as the mean ± SEM. t = 3.6; df = 82; * p = 0.0001.
Mentions: When mice enter the center or choice point of the plus maze, they have the option of continuing straight into the opposite arm or turning into either the left or right arm [11]. Wild-type (n = 10) and HIP14 knockout mice (n = 10) participated in multiple recording sessions; each mouse participated in at least two sessions for a total of 38 and 46 sessions, respectively, for each group. As Figure 1 shows, wild-type mice turn to explore the perpendicular arms with a probability of 0.71 ± 0.01. In contrast, HIP14 knockout mice are less likely to turn (the probability of turning is 0.60 ± 0.02); instead, once they cross the choice point, they explore the opposite arm. Statistical analysis of the probability of turning revealed a significant difference between wild-type and HIP14 knockout mice (t = 3.6, degrees of freedom (df) = 82, p = 0.0005).

Bottom Line: Striatal LFP activity anticipates this difference.In wild-types, the power spectral density pattern associated with entry into the choice point differs significantly from the pattern immediately before entry, especially at low frequencies (≤13 Hz), whereas HIP14 knockouts show no change in LFP activity as they enter the choice point.Our results suggest that HIP14 plays a critical role in the aberrant behavioral modulation of striatal neuronal activity underlying motor inflexibility, including the motor signs of HD.

View Article: PubMed Central - PubMed

Affiliation: Program in Neuroscience, Indiana University, Bloomington, IN 47405, USA.

ABSTRACT
Huntington's disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, impairs information processing in the striatum, which, as part of the basal ganglia, modulates motor output. Growing evidence suggests that huntingtin interacting protein 14 (HIP14) contributes to HD neuropathology. Here, we recorded local field potentials (LFPs) in the striatum as HIP14 knockout mice and wild-type controls freely navigated a plus-shaped maze. Upon entering the choice point of the maze, HIP14 knockouts tend to continue in a straight line, turning left or right significantly less often than wild-types, a sign of motor inflexibility that also occurs in HD mice. Striatal LFP activity anticipates this difference. In wild-types, the power spectral density pattern associated with entry into the choice point differs significantly from the pattern immediately before entry, especially at low frequencies (≤13 Hz), whereas HIP14 knockouts show no change in LFP activity as they enter the choice point. The lack of change in striatal activity may explain the turning deficit in the plus maze. Our results suggest that HIP14 plays a critical role in the aberrant behavioral modulation of striatal neuronal activity underlying motor inflexibility, including the motor signs of HD.

No MeSH data available.


Related in: MedlinePlus