scholarly journals Bdnf promoter IV-expressing cells in the hippocampus modulate fear expression and hippocampal-prefrontal synchrony in mice

2019 ◽  
Author(s):  
Henry L. Hallock ◽  
Henry M. Quillian ◽  
Yishan Mai ◽  
Kristen R. Maynard ◽  
Julia L. Hill ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Plasticity ◽  
Neurotrophic Factor ◽  
Memory Retrieval ◽  
Cell Types ◽  
Fear Memory ◽  
Brain Derived Neurotrophic Factor ◽  
Bdnf Signaling ◽  
Fear Expression

AbstractBrain-derived neurotrophic factor (BDNF) signaling regulates synaptic plasticity in the hippocampus (HC) and prefrontal cortex (PFC), and has been extensively linked with fear memory expression in rodents. Notably, disrupting BDNF production from promoter IV-derived transcripts enhances fear expression in mice, and decreases fear-associated HC-PFC synchrony, suggesting that Bdnf transcription from promoter IV plays a key role in HC-PFC function during fear memory retrieval. To understand how promoter IV-derived BDNF affects fear expression and HC-PFC connectivity, we generated a viral construct that selectively targets cells expressing promoter IV-derived Bdnf transcripts (“p4-cells”) for tamoxifen-inducible Cre-mediated recombination (AAV8-p4Bdnf-ERT2CreERT2-PEST). Using this construct, we found that ventral (vHC) p4-cells are recruited during fear expression, and that activation of these cells causes exaggerated fear expression that co-occurs with disrupted vHC-PFC synchrony in mice. Our data highlight how this novel construct can be used to interrogate genetically-defined cell types that selectively contribute to BDNF-dependent behaviors.

scholarly journals Brain-derived neurotrophic factor differentially modulates excitability of two classes of hippocampal output neurons

2016 ◽  
Vol 116 (2) ◽  
pp. 466-471 ◽  
Author(s):  
A. R. Graves ◽  
S. J. Moore ◽  
N. Spruston ◽  
A. K. Tryba ◽  
C. C. Kaczorowski
Keyword(s):  
Synaptic Plasticity ◽  
Neurotrophic Factor ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Cell Types ◽  
Brain Derived Neurotrophic Factor ◽  
The Other ◽  
Morphological Properties ◽  
Intrinsic Plasticity ◽  
The Brain

Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampus-dependent learning and memory. Canonically, this has been ascribed to an enhancing effect on neuronal excitability and synaptic plasticity in the CA1 region. However, it is the pyramidal neurons in the subiculum that form the primary efferent pathways conveying hippocampal information to other areas of the brain, and yet the effect of BDNF on these neurons has remained unexplored. We present new data that BDNF regulates neuronal excitability and cellular plasticity in a much more complex manner than previously suggested. Subicular pyramidal neurons can be divided into two major classes, which have different electrophysiological and morphological properties, different requirements for the induction of plasticity, and different extrahippocampal projections. We found that BDNF increases excitability in one class of subicular pyramidal neurons yet decreases excitability in the other class. Furthermore, while endogenous BDNF was necessary for the induction of synaptic plasticity in both cell types, BDNF enhanced intrinsic plasticity in one class of pyramidal neurons yet suppressed intrinsic plasticity in the other. Taken together, these data suggest a novel role for BDNF signaling, as it appears to dynamically and bidirectionally regulate the output of hippocampal information to different regions of the brain.

scholarly journals Modulation of Brain-Derived Neurotrophic Factor (BDNF) Signaling Pathway by Culinary Sage (Salvia officinalis L.)

2021 ◽  
Vol 22 (14) ◽  
pp. 7382
Author(s):  
Nancy Chiang ◽  
Shahla Ray ◽  
Jade Lomax ◽  
Sydney Goertzen ◽  
Slavko Komarnytsky ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Neurotrophic Factor ◽  
High Performance ◽  
Memory Function ◽  
Brain Derived Neurotrophic Factor ◽  
Salvia Officinalis ◽  
C6 Glioma Cells ◽  
Medicinal Uses ◽  
Bdnf Signaling ◽  
Salvia Officinalis L

Culinary sage (Salvia officinalis L.) is a common spice plant in the mint family (Lamiaceae) well known for its distinctive culinary and traditional medicinal uses. Sage tea has been used traditionally as a brain-enhancing tonic and extracts from sage have been reported to have both cognitive and memory enhancing effects. Brain-derived neurotrophic factor (BDNF) is an endogenous signaling molecule involved in cognition and memory function. In this study, activity-guided fractionation employing preparative reverse-phase high performance liquid chromatography (RP-HPLC) of culinary sage extracts led to the discovery of benzyl 6-O-β-D-apiofuranosyl-β-D-glucoside (B6AG) as a natural product that upregulates transcription of neurotrophic factors in C6 glioma cells. Purified B6AG showed a moderate dose response, with upregulation of BDNF and with EC50 at 6.46 μM. To better understand the natural variation in culinary sage, B6AG was quantitated in the leaves of several commercial varieties by liquid chromatography-mass spectrometry (LC-MS). The level of B6AG in dried culinary sage was found to range from 334 ± 14 to 698 ± 65 μg/g. This study provided a foundation for future investigations, including quantitative inquiries on the distribution of B6AG within the different plant organs, explorations in optimizing post-harvest practices, and aid in the development of sage varieties with elevated levels of B6AG.

Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions

2016 ◽  
Vol 131 (2) ◽  
pp. 123-138 ◽  
Author(s):  
Veronica Begni ◽  
Marco Andrea Riva ◽  
Annamaria Cattaneo
Keyword(s):  
Synaptic Plasticity ◽  
Stress Response ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Brain Derived Neurotrophic Factor ◽  
Mitogen Activated Protein Kinase ◽  
Bdnf Expression ◽  
Pathological Conditions ◽  
Wide Range

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in the central nervous system, promoting synaptic plasticity, neurogenesis and neuroprotection. The BDNF gene structure is very complex and consists of multiple 5′-non-coding exons, which give rise to differently spliced transcripts, and one coding exon at the 3′-end. These multiple transcripts, together with the complex transcriptional regulatory machinery, lead to a complex and fine regulation of BDNF expression that can be tissue and stimulus specific. BDNF effects are mainly mediated by the high-affinity, tropomyosin-related, kinase B receptor and involve the activation of several downstream cascades, including the mitogen-activated protein kinase, phospholipase C-γ and phosphoinositide-3-kinase pathways. BDNF exerts a wide range of effects on neuronal function, including the modulation of activity-dependent synaptic plasticity and neurogenesis. Importantly, alterations in BDNF expression and function are involved in different brain disorders and represent a major downstream mechanism for stress response, which has important implications in psychiatric diseases, such as major depressive disorders and schizophrenia. In the present review, we have summarized the main features of BDNF in relation to neuronal plasticity, stress response and pathological conditions, and discussed the role of BDNF as a possible target for pharmacological and non-pharmacological treatments in the context of psychiatric illnesses.

scholarly journals Brain-Derived Neurotrophic Factor-Induced Gene Expression Reveals Novel Actions of VGF in Hippocampal Synaptic Plasticity

2003 ◽  
Vol 23 (34) ◽  
pp. 10800-10808 ◽  
Author(s):  
Janet Alder ◽  
Smita Thakker-Varia ◽  
Debra A. Bangasser ◽  
May Kuroiwa ◽  
Mark R. Plummer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synaptic Plasticity ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Hippocampal Synaptic Plasticity
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