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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: Growing evidence suggests that huntingtin interacting protein 14 (HIP14) contributes to HD neuropathology.Striatal LFP activity anticipates this difference.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

Striatal PSD immediately before the choice point (A) and after arm entry (B) for wild-type (black) and HIP14 knockout mice (red). In each case, data are based on one second of LFP activity obtained from 50 random events per recording session (43 wild-type and 44 HIP14-knockout sessions). Dashed boxes denote the frequencies at which the mean PSD significantly differ. Data are expressed as the mean ± SEM (p ≤ 0.05). Insert: close up of frequencies at which differences were observed.
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brainsci-03-01588-f004: Striatal PSD immediately before the choice point (A) and after arm entry (B) for wild-type (black) and HIP14 knockout mice (red). In each case, data are based on one second of LFP activity obtained from 50 random events per recording session (43 wild-type and 44 HIP14-knockout sessions). Dashed boxes denote the frequencies at which the mean PSD significantly differ. Data are expressed as the mean ± SEM (p ≤ 0.05). Insert: close up of frequencies at which differences were observed.

Mentions: As shown in Figure 4, we also compared choice-related and arm-related LFP activity between wild-type and HIP14 knockout mice. Striatal LFPs in HIP14 knockout mice relative to wild-type show significant increases in delta (0.1–4 Hz) and alpha (8–13 Hz) frequencies and decreases in beta (13–30 Hz) immediately before the choice point, but increases in the theta (4–7 Hz) and alpha (8–13 Hz) range after arm entry.


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)

Striatal PSD immediately before the choice point (A) and after arm entry (B) for wild-type (black) and HIP14 knockout mice (red). In each case, data are based on one second of LFP activity obtained from 50 random events per recording session (43 wild-type and 44 HIP14-knockout sessions). Dashed boxes denote the frequencies at which the mean PSD significantly differ. Data are expressed as the mean ± SEM (p ≤ 0.05). Insert: close up of frequencies at which differences were observed.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

brainsci-03-01588-f004: Striatal PSD immediately before the choice point (A) and after arm entry (B) for wild-type (black) and HIP14 knockout mice (red). In each case, data are based on one second of LFP activity obtained from 50 random events per recording session (43 wild-type and 44 HIP14-knockout sessions). Dashed boxes denote the frequencies at which the mean PSD significantly differ. Data are expressed as the mean ± SEM (p ≤ 0.05). Insert: close up of frequencies at which differences were observed.
Mentions: As shown in Figure 4, we also compared choice-related and arm-related LFP activity between wild-type and HIP14 knockout mice. Striatal LFPs in HIP14 knockout mice relative to wild-type show significant increases in delta (0.1–4 Hz) and alpha (8–13 Hz) frequencies and decreases in beta (13–30 Hz) immediately before the choice point, but increases in the theta (4–7 Hz) and alpha (8–13 Hz) range after arm entry.

Bottom Line: Growing evidence suggests that huntingtin interacting protein 14 (HIP14) contributes to HD neuropathology.Striatal LFP activity anticipates this difference.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