In vivo BDNF modulation of hippocampal mossy fiber plasticity induced by high frequency stimulation

Abstract

Changes in synaptic efficacy and morphology have been proposed as mechanisms underlying learning and memory processes. In our previous studies, high frequency stimulation (HFS) sufficient to induce LTP at the hippocampal mossy fiber (MF) pathway, leads to MF synaptogenesis, in a prominent contralateral form, at the stratum oriens of hippocampal CA3 area. Recently we reported that acute intrahippocampal microinfusion of BDNF induces a lasting potentiation of synaptic efficacy at the MF projection accompanied by a structural reorganization at the CA3 area within the stratum oriens region in a prominent ipsilateral form. It is considered that the capacity of synapses to express plastic changes is itself subject to variation dependent on previous experience. Here we used intrahippocampal microinfusion of BDNF to analyze its effects on functional and structural synaptic plasticity induced by subsequent mossy fiber HFS sufficient to induce LTP in adult rats, in vivo. Our results show that BDNF modifies the ability of the MF pathway to present LTP by HFS. Moreover BDNF modified the structural reorganization pattern produced by HFS, presenting a balanced bilateral appearance. Microinfusion of K252a blocks the functional and morphological effects produced by BDNF, revealing that the BDNF modulation is dependent on its TrkB receptor activation. These findings support the idea that BDNF actions modify subsequent synaptic plasticity; a homeostatic mechanism thought to be essential for synaptic integration among prolonged temporal domains in the adult mammalian brain.

Coexistence of Multiple Types of Synaptic Plasticity in Individual Hippocampal CA1 Pyramidal Neurons

“…In this respect, a large body of evidence stresses the important role of ACh, DA, intracellular cAMP elevation and BDNF signaling, respectively, in gating, facilitating or even mediating signaling events leading to synaptic plasticity (see e.g., cAMP: Otmakhova et al, 2000; DA/cAMP: Navakkode et al, 2010; Sheynikhovich et al, 2013; Otani et al, 2015; ACh: Nakauchi and Sumikawa, 2012; BDNF: Sivakumaran et al, 2009; Schjetnan and Escobar, 2012; Schildt et al, 2013, compare Figure 2). These same neuromodulators were also reported to be essential for establishing STDP (see e.g., ACh: Couey et al, 2007; Goriounova and Mansvelder, 2012; NA/ACh: Seol et al, 2007; DA: Pawlak and Kerr, 2008; Zhang et al, 2009; Edelmann and Lessmann, 2011, 2013; Cassenaer and Laurent, 2012; Yang and Dani, 2014; endocannabinoids (eCB): Cui et al, 2015, 2016; BDNF: Edelmann et al, 2015; Monoamines: He et al, 2015; compare Figure 1).…”

Non-invasive Brain Stimulation in the Treatment of Post-stroke and Neurodegenerative Aphasia: Parallels, Differences, and Lessons Learned

“…In part, this move toward exploring the use of non-invasive neuomodulation is fueled by an increasing understanding of the mechanisms that drive abnormal structural and functional organization of the brain in psychiatric and neurologic disease, and an increasing realization that improved characterization of these mechanisms affords greater opportunities for focused intervention. Clinically-oriented discoveries in systems-level neuroscience have led to a sea change in the conceptualization of a variety of disease processes such as depression (Boggio et al, 2008; Brunoni et al, 2011, 2012), dementia syndromes (Freitas et al, 2011; Elder and Taylor, 2014), traumatic brain injury (Demirtas-Tatlidede et al, 2012), and focal deficits after stroke (Schjetnan and Escobar, 2012; Blesneag et al, 2015), not simply as problems with specific regions of the brain, but as problems with brain networks, the treatment of which is directly linked to the ability to harness and modulate the brains' capacity for functional reorganization.…”

Contrasting hippocampal and amygdalar expression of genes related to neural plasticity during escape from social aggression

“…The behaviors associated with conditioned defeat are enhanced by overexpression of CREB in the basolateral amygdala (BLA) [27]. Neurotrophins such as brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin related kinase B (TrK B ) as well as the AMPA receptor subunit GluR 1 contribute to molecular mechanisms of neural plasticity such as long-term potentiation, synaptic remodeling, and changes in learning [23,28–30]. What is more, BDNF and TrK B in the hippocampus and amygdala appear to be important for social defeat conditioning [31,32].…”