Spontaneous glutamatergic activity induces a BDNF‐dependent potentiation of GABAergic synapses in the newborn rat hippocampus

Abstract

Spontaneous ongoing synaptic activity is thought to play an instructive role in the maturation of the neuronal circuits. However the type of synaptic activity involved and how this activity is translated into structural and functional changes is not fully understood. Here we show that ongoing glutamatergic synaptic activity triggers a long-lasting potentiation of γ-aminobutyric acid (GABA) mediated synaptic activity (LLP GABA-A ) in the developing rat hippocampus. LLP GABA-A induction requires (i) the activation of AMPA receptors and L-type voltage-dependent calcium channels, (ii) the release of endogenous brain-derived neurotrophic factor (BDNF), and (iii) the activation of postsynaptic tropomyosin-related kinase receptors B (TrkB). We found that spontaneous glutamatergic activity is required to maintain a high level of native BDNF in the newborn rat hippocampus and that application of exogenous BDNF induced LLP GABA-A in the absence of glutamatergic activity. These results suggest that ongoing glutamatergic synaptic activity plays a pivotal role in the functional maturation of hippocampal GABAergic synapses by means of a cascade involving BDNF release and downstream signalling through postsynaptic TrkB receptor activation.

Increase of hippocampal glutamate after electroconvulsive treatment: A quantitative proton MR spectroscopy study at 9.4 T in an animal model of depression

“…Due to a dynamic equilibrium of GABA and glutamate (Mathews and Diamond 2003), an increase of intracellular glutamate should precede an increase of intracellular GABA. Additionally, glutamatergic activity could stimulate GABAergic synaptogenesis and thus enhance GABAergic tone (Kuczewski et al 2008;Sivakumaran et al 2009). Therefore, the increase of glutamate after an acute ECS treatment in cLH and WT rats could refl ect several effects of this treatment, including an increase of glutamatergic or GABAergic activity, as well as altered glucose metabolism.…”

Activity-Dependent Regulation of Synapses by Retrograde Messengers

“…BDNF-GFP) have established that growth factors are present in secretory granules within dendrites (Kohara et al, 2001) and that high-frequency stimulation evokes BDNF release from the dendrites of neurons in a calcium-dependent manner (Hartmann et al, 2001). High-frequency firing of the postsynaptic cell evokes BDNF release, whereas synaptic activation alone does not (Kuczewski et al, 2008a; Kuczewski et al, 2008b; Kuczewski et al, 2009). An interesting and potentially important aspect of BDNF release is that it can be rather slow and persist for minutes after depolarization of the postsynaptic cell (Kuczewski et al, 2008b).…”

Impaired transmission at corticothalamic excitatory inputs and intrathalamic GABAergic synapses in the ventrobasal thalamus of heterozygous BDNF knockout mice

“…Chronic action of BDNF in hippocampus and neocortex regulates the efficacy of GABAergic synapses either by enhancing formation of presynaptic terminals or increasing presynaptic release probability (see e.g., Baldelli et al, 2005;Kohara et al, 2007). Importantly, also endogenously released BDNF has been shown to regulate GABAergic synaptic transmission in the hippocampus (Gubellini et al, 2005;Kohara et al, 2007;Kuczewski et al, 2008), thus stressing the physiological importance of BDNF signaling also for GABAergic synapses.…”