Learning deficits in forebrain-restricted brain-derived neurotrophic factor mutant mice

Gorski, Jessica A.; Balogh, Seth A.; Wehner, Jeanne M.; Jones, Kevin R.

doi:10.1016/s0306-4522(03)00426-3

Cited by 201 publications

(164 citation statements)

References 78 publications

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…Second, disrupting activity-dependent BDNF does not alter the acquisition or consolidation of hippocampal-dependent spatial and contextual memories. This finding is surprising because reduction of basal BDNF expression has been shown to impair hippocampal-dependent learning and memory (31)(32)(33)(34). Thus, our results underscore the distinct functions of constitutive versus activity-dependent BDNF expression.…”

Section: Discussionmentioning

confidence: 64%

Role of activity-dependent BDNF expression in hippocampal–prefrontal cortical regulation of behavioral perseverance

Sakata

Martinowich²,

Woo

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

119

131

View full text Add to dashboard Cite

Activity-dependent gene transcription, including that of the brainderived neurotrophic factor (Bdnf) gene, has been implicated in various cognitive functions. We previously demonstrated that mutant mice with selective disruption of activity-dependent BDNF expression (BDNF-KIV mice) exhibit deficits in GABA-mediated inhibition in the prefrontal cortex (PFC). Here, we show that disruption of activity-dependent BDNF expression impairs BDNF-dependent late-phase long-term potentiation (L-LTP) in CA1, a site of hippocampal output to the PFC. Interestingly, early-phase LTP and conventional L-LTP induced by strong tetanic stimulation were completely normal in BDNF-KIV mice. In parallel, attenuation of activity-dependent BDNF expression significantly impairs spatial memory reversal and contextual memory extinction, two executive functions that require intact hippocampal-PFC circuitry. In contrast, spatial and contextual memory per se were not affected. Thus, activity-dependent BDNF expression in the hippocampus and PFC may contribute to cognitive and behavioral flexibility. These results suggest distinct roles for different forms of L-LTP and provide a link between activity-dependent BDNF expression and behavioral perseverance, a hallmark of several psychiatric disorders.

show abstract

Section: Discussionmentioning

confidence: 64%

Role of activity-dependent BDNF expression in hippocampal–prefrontal cortical regulation of behavioral perseverance

Sakata

Martinowich²,

Woo

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

119

131

View full text Add to dashboard Cite

show abstract

“…Nevertheless, PC7 KO mice are mildly deficient in response plasticity on this test, suggestive of some hippocampal abnormalities. Other investigators have noted that water maze performance is perturbed in forebrain-deleted BDNF mice (35) and in mice with hippocampal virally induced BDNF ablation (34), whereas transgenic overexpression of BDNF in the cerebral cortex and hippocampus facilitates performance (36). The basis for the discrepancy between these and our ) with vehicle (CTL) or 0.7 mg/kg DHF.…”

Section: Discussionmentioning

confidence: 72%

“…Moreover, these mutants are impaired not only in contextual and cued fear conditioning but also in FPS. Other investigators have reported that BDNF +/− , BDNF Met/Met , and forebrain-inducible BDNFdeleted mice are impaired in contextual fear conditioning, whereas cued conditioning is retained (35,(43)(44)(45). Cued fear conditioning, however, can be deficient in older BDNF +/− animals (46).…”

Section: Discussionmentioning

confidence: 99%

“…Ten-micrometer-thick cryosections were prepared from brains of 3-mo-old mice, fixed in 4% formaldehyde, and hybridized as previously described (49) with mouse sense (negative control) and antisense cRNA probes. The latter probes corresponded to the mouse PC7 or mouse BDNF coding regions for residues 1-213 or residues 25-117, respectively, and were synthesized using 35 S-UTP (PerkinElmer).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice

Wetsel

Rodriguiz

Guillemot

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

PC7 belongs to the proprotein convertase family, whose members are implicated in the cleavage of secretory precursors. The in vivo function of PC7 is unknown. Herein, we find that the precursor proBDNF is processed into mature BDNF in COS-1 cells coexpressing proBDNF with either PC7 or Furin. Conversely, the processing of proBDNF into BDNF is markedly reduced in the absence of either Furin or PC7 in mouse primary hepatocytes. In vivo we observe that BDNF and PC7 mRNAs are colocalized in mouse hippocampus and amygdala and that mature BDNF protein levels are reduced in these brain areas in PC7 KO mice but not in the hippocampus of PC1/3 KO mice. Various behavioral tests reveal that in PC7 KO mice spatial memory is intact and plasticity of responding is mildly abnormal. Episodic and emotional memories are severely impaired, but both are rescued with the tyrosine receptor kinase B agonist 7,8-dihydroxyflavone. Altogether, these results support an in vivo role for PC7 in the regulation of certain types of cognitive performance, in part via proBDNF processing. Because polymorphic variants of human PC7 are being characterized, it will be important in future studies to determine their effects on additional physiological and behavioral processes.

show abstract

“…Previous studies in animals and humans demonstrate an association between BDNF genotype and hippocampus morphology, function, and neurochemistry. Restricted BDNF mutant mice without BDNF in the dorsal cortex and hippocampus failed to learn a hippocampus-dependent memory task (Gorski et al, 2003). Moreover, knockout mice with reduced BDNF expression in the cortex and hippocampus showed approximately 70% reduction of BDNF protein level in the hippocampus accompanied by impairment in hippocampal-dependent learning and long-term potentiation (Monteggia et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

Matsuo

Walss‐Bass

Nery

et al. 2009

Neuropsychopharmacol

112

View full text Add to dashboard Cite

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been proposed as a possible candidate for involvement in the pathophysiology of bipolar disorder (BD). To determine whether an association exists between the BDNF Val66Met genotype and morphometric abnormalities of the brain regions involved in memory and learning in BD and healthy subjects. Forty-two BD patients and 42 healthy subjects were studied. Interactions between BDNF Val66Met genotype and diagnosis in gray (GM) volumes were analyzed using an optimized voxel-based morphometry technique. Declarative memory function was assessed with the California Verbal Learning Test II. Left and right anterior cingulate GM volumes showed a significant interaction between genotype and diagnosis such that anterior cingulate GM volumes were significantly smaller in the Val/Met BD patients compared with the Val/Val BD patients (left P ¼ 0.01, right P ¼ 0.01). Within-group comparisons revealed that the Val/Met carriers showed smaller GM volumes of the dorsolateral prefrontal cortex compared with the Val/Val subjects within the BD patient (P ¼ 0.01) and healthy groups (left P ¼ 0.03, right P ¼ 0.03). The Val/ Met healthy subjects had smaller GM volumes of the left hippocampus compared with the Val/Val healthy subjects (Po0.01). There was a significant main effect of diagnosis on memory function (P ¼ 0.04), but no interaction between diagnosis and genotype was found (P ¼ 0.48). The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD.

show abstract

Learning deficits in forebrain-restricted brain-derived neurotrophic factor mutant mice

Cited by 201 publications

References 78 publications

Role of activity-dependent BDNF expression in hippocampal–prefrontal cortical regulation of behavioral perseverance

Role of activity-dependent BDNF expression in hippocampal–prefrontal cortical regulation of behavioral perseverance

Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

Contact Info

Product

Resources

About