Reduced hippocampal neurogenesis and skill reaching performance in adult Emx1 mutant mice

Hong, Shwuhuey; Liu, Zhengyan; Yang, Fan; Neumann, Melanie; Won, Seok Joon; Lac, Diana; Lum, Xuanmin; Weinstein, Philip; Liu, Jialing

doi:10.1016/j.expneurol.2007.03.028

Cited by 40 publications

(40 citation statements)

References 42 publications

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“…In addition to the primary motor cortex 6,7,19,23 , many other brain regions such as the substantial nigra and ventral tegmental area 16,24 , striatum 25 , and hippocampus 26 have been suggested to also play important roles in the single seed reaching task introduced here. Therefore, the single seed reaching task may be useful to study many discriminatory regions of the rodent brain associated with motor learning.…”

Section: Circuitry For Motor Learning and Memorymentioning

confidence: 99%

Study Motor Skill Learning by Single-pellet Reaching Tasks in Mice

Chen

Gilmore

Zuo

2014

JoVE

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Reaching for and retrieving objects require precise and coordinated motor movements in the forelimb. When mice are repeatedly trained to grasp and retrieve food rewards positioned at a specific location, their motor performance (defined as accuracy and speed) improves progressively over time, and plateaus after persistent training. Once such reaching skill is mastered, its further maintenance does not require constant practice. Here we introduce a single-pellet reaching task to study the acquisition and maintenance of skilled forelimb movements in mice. In this video, we first describe the behaviors of mice that are commonly encountered in this learning and memory paradigm, and then discuss how to categorize these behaviors and quantify the observed results. Combined with mouse genetics, this paradigm can be utilized as a behavioral platform to explore the anatomical underpinnings, physiological properties, and molecular mechanisms of learning and memory. Video LinkThe video component of this article can be found at

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Section: Circuitry For Motor Learning and Memorymentioning

confidence: 99%

Study Motor Skill Learning by Single-pellet Reaching Tasks in Mice

Chen

Gilmore

Zuo

2014

JoVE

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“…[37][38][39][40] Specifically, mice (n = 20 per group) were placed on a rotating rod that accelerated 5 rpm every 15 sec with a maximum speed of 40 rpm, and the length of time that the mouse remained on the rod (fall latency) was recorded and averaged for five consecutive trials with 5-min intervals between trials. The trials were repeated on three separate days.…”

Section: Behavioral Studiesmentioning

confidence: 99%

“…Spatial learning and memory were evaluated by using the Morris water maze, 35,[37][38][39][40][41] starting at eight weeks after TBI or sham surgery. 38,[40][41][42][43][44] Mice (n = 12 per group) were trained to locate a platform in opaque water in a circular pool (135 cm diameter) during two successive daily sessions (three trials per session, 60 sec per trial) with a 1-h intersession interval.…”

Section: Behavioral Studiesmentioning

confidence: 99%

“…37,38,40,41 Individual mice (n = 20 per group) were placed in a brightly lit, square Plexiglas enclosure (40 · 40 inches) surrounded by automated infrared photocells that interfaced with a computer (Hamilton & Kinder) to record data. Beam breaks generated by movement were monitored, allowing measurements of the number of basic movements and total path length traveled during the exploration.…”

Section: Behavioral Studiesmentioning

confidence: 99%

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CCR2 Deficiency Impairs Macrophage Infiltration and Improves Cognitive Function after Traumatic Brain Injury

Hsieh

Niemi

Wang

et al. 2014

Journal of Neurotrauma

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144

138

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Traumatic brain injury (TBI) provokes inflammatory responses, including a dramatic rise in brain macrophages in the area of injury. The pathway(s) responsible for macrophage infiltration of the traumatically injured brain and the effects of macrophages on functional outcomes are not well understood. C-C-chemokine receptor 2 (CCR2) is known for directing monocytes to inflamed tissues. To assess the role of macrophages and CCR2 in TBI, we determined outcomes in CCR2-deficient (Ccr2 -/ -) mice in a controlled cortical impact model. We quantified brain myeloid cell numbers post-TBI by flow cytometry and found that Ccr2 -/ -mice had greatly reduced macrophage numbers (*80-90% reduction) early post-TBI, compared with wild-type mice. Motor, locomotor, and cognitive outcomes were assessed. Lack of Ccr2 improved locomotor activity with less hyperactivity in open field testing, but did not affect anxiety levels or motor coordination on the rotarod three weeks after TBI. Importantly, Ccr2-/ -mice demonstrated greater spatial learning and memory, compared with wildtype mice eight weeks after TBI. Although there was no difference in the volume of tissue loss, Ccr2 -/ -mice had significantly increased neuronal density in the CA1-CA3 regions of the hippocampus after TBI, compared with wild-type mice. These data demonstrate that Ccr2 directs the majority of macrophage homing to the brain early after TBI and indicates that Ccr2 may facilitate harmful responses. Lack of Ccr2 improves functional recovery and neuronal survival. These results suggest that therapeutic blockade of CCR2-dependent responses may improve outcomes following TBI.

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“…It encodes a transcription factor important for brain development. 14,15 We found the fetal brain enhancers 11 270 and 5866 to reside in EXOC6B and both are covered by the smallest ID-associated microdeletions; the translocation breakpoints are located between these brain enhancers and EMX1 (Supplementary Figure 3). 9,11 We hypothesize that deletion of enhancers or translocation to another region changed the regulatory environment of EMX1 and resulted in dysregulated EMX1 expression in the ID-affected individuals, providing further evidence for involvement of EXOC6B in SEMD.…”

Section: Resultsmentioning

confidence: 89%

A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene

et al. 2015

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We report two brothers from a consanguineous couple with spondyloepimetaphyseal dysplasia (SEMD), multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones, probably representing a yet uncharacterized SEMD with laxity and dislocations. This condition has clinical overlap with autosomal dominantly inherited SEMD with joint laxity, leptodactylic type caused by recurrent missense variants in the kinesin family member 22 gene (KIF22). Single-nucleotide polymorphism array analysis and whole-exome sequencing in the two affected siblings revealed a shared homozygous nonsense variant [c.906T4A/p.(Tyr302*)] in EXOC6B as the most likely cause. EXOC6B encodes a component of the exocyst complex required for tethering secretory vesicles to the plasma membrane. As transport of vesicles from the golgi apparatus to the plasma membrane occurs through kinesin motor proteins along microtubule tracks, the function of EXOC6B is linked to KIF22 suggesting a common pathogenic mechanism in skeletal dysplasias with joint laxity and dislocations. INTRODUCTIONSkeletal dysplasias with multiple joint dislocations is a heterogeneous group of disorders comprising~10 distinct entities. 1 Spondyloepimetaphyseal dysplasia (SEMD) with joint laxity type 2 (leptodactylic type, Hall type or SEMD-JL2; MIM 603546) is an autosomal dominant skeletal dysplasia with short stature, multiple joint dislocations and/or laxity, delayed ossification of carpals, small carpus, severe epiphyseal and mild metaphyseal changes, mild vertebral body deformities and gracile metacarpals. 2 Missense variants affecting one of two amino acids in the motor domain of the kinesin family member KIF22 have been identified to cause SEMD-JL2. 3,4 Key features of SEMD with joint laxity, type 1, with or without fractures (SEMD-JL1; MIM 271640), which is caused by biallelic variants in B3GALT6, 5,6 are joint laxity and dislocations and SEMD. Affected individuals show facial dysmorphism, kyphoscoliosis at birth, talipes equinovarus, cleft palate and congenital heart disease. 7 Another SEMD-JL2-like phenotype is associated with a homozygous missense variant in NIN. 8 Here, we report two brothers with a new type of autosomal recessive SEMD with laxity and joint dislocations. We used single-nucleotide polymorphism (SNP) array analysis and whole-exome sequencing (WES) to identify a homozygous nonsense variant in EXOC6B in the affected siblings.

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Reduced hippocampal neurogenesis and skill reaching performance in adult Emx1 mutant mice

Cited by 40 publications

References 42 publications

Study Motor Skill Learning by Single-pellet Reaching Tasks in Mice

Study Motor Skill Learning by Single-pellet Reaching Tasks in Mice

CCR2 Deficiency Impairs Macrophage Infiltration and Improves Cognitive Function after Traumatic Brain Injury

A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene

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