High-frequency stimulation-induced synaptic potentiation in dorsal and ventral CA1 hippocampal synapses: the involvement of NMDA receptors, mGluR5, and (L-type) voltage-gated calcium channels

Abstract

The ability of the ventral hippocampus (VH) for long-lasting long-term potentiation (LTP) and the mechanisms underlying its lower ability for short-lasting LTP compared with the dorsal hippocampus (DH) are unknown. Using recordings of field excitatory postsynaptic potentials (EPSPs) from the CA1 field of adult rat hippocampal slices, we found that 200-Hz stimulation induced nondecremental LTP that was maintained for at least 7 h and was greater in the DH than in the VH. The interaction of NMDA receptors with L-type voltage-dependent calcium channels appeared to be more effective in the DH than in the VH. Furthermore, the LTP was significantly enhanced in the DH only, between 2 and 5 h post-tetanus. Furthermore, the mGluR5 contributed to the post-tetanic potentiation more in the VH than in the DH.The hippocampus is a brain structure with paramount capacity for phenomena of short-term and long-term synaptic plasticity (Bliss et al. 2007). Remarkably, this ability is not uniformly distributed along the long axis of the structure. Namely, the ability for longterm potentiation (LTP) induced by high-frequency stimulation (HFS) is strikingly lower in the ventral hippocampus (VH) compared with the dorsal hippocampus (DH) (Papatheodoropoulos and Kostopoulos 2000;Maruki et al. 2001;Colgin et al. 2004;Maggio and Segal 2009;Kenney and Manahan-Vaughan 2013;Keralapurath et al. 2014). This is one of the most notable differences recently found in the intrinsic circuitry between the DH and the VH. Long-term synaptic plasticity is thought to be a fundamental mechanism that supports learning and memory (Matynia et al. 2002;Takeuchi et al. 2014). Thus, differences in the ability for LTP induction might contribute to the well-known functional segregation along the long (dorsoventral or septotemporal) axis of the hippocampus (Moser and Moser 1998;Fanselow and Dong 2010;Bast 2011;Goosens 2011;Small et al. 2011;Bannerman et al. 2014;Strange et al. 2014). Despite the established difference in the magnitude of HFS-induced LTP between the two hippocampus segments, the underlying mechanisms remain unknown. This is because, although HFS-induced LTP can be blocked by antagonists of NMDARs (Park et al. 2014), HFS might induce compound LTP in the CA1 field with the participation of L-type voltage-dependent calcium channels (L-VDCCs), (Grover and Teyler 1990;Cavus and Teyler 1996;Morgan and Teyler 2001;Bayazitov et al. 2007) and of metabotropic glutamate receptor-5 (mGluR5) (Jia et al. 1998). NMDAR-dependent and L-VDCC-dependent LTP might have distinct implication in certain types of learning and memory (Morris et al. 1986;Tsien et al. 1996;Borroni et al. 2000;Moosmang et al. 2005). In addition, NMDAR-LTP and L-VDCC-LTP might preferentially be involved in retention of information over short and long periods of time, respectively (Borroni et al. 2000).A parameter of LTP particularly relevant for the implications of LTP in the memory function is the persistence of potentiation (Martin et al. 2000;Lynch 2004). Nondecremental LTP lasting for severa...

Distinct Properties of Long-Term Potentiation in the Dentate Gyrus along the Dorsoventral Axis: Influence of Age and Inhibition

“…Strikingly, this difference was found to be almost faded away in middle-aged (9–12 months old) animals, apparently due to a decline in strength of ventral LTP to a similar magnitude as dorsal LTP. The larger ventral DG-LTP is diametrically opposed to studies in the CA1 region, where the dorsal segment has been reported to have a higher ability to undergo LTP 10 – 14 . In accordance with a dorsoventral gradient rather than a clear-cut segregation, our LTP data of the intermediate segment fall right in between those of dorsal and ventral slices, supporting the presence of an intermediate region that expresses “partly overlapping characteristics with its neighbour regions”, as proposed by Fanselow and Dong (2010) 1 .…”

“…Furthermore, the subunits of AMPA and NMDA glutamate receptors, important postsynaptic components in synaptic plasticity, are differentially distributed along the dorsoventral axis in the rat hippocampus 23 . Several other channels that are important for intrinsic excitability are also differentially expressed or activated along the dorsoventral axis 14 , 24 – 27 . This results in decisive differences in neuronal parameters which control the excitability and firing properties, and hence the basal input/output properties and LTP magnitude obtained in response to particular induction protocols 13 , 25 , 28 .…”

A method to induce human cortical long-term potentiation by acoustic stimulation

“…Subsequently, a classic in vitro model was established for investigating LTP based on the acute hippocampal slice, which is widely used due to its simplified neural circuits and relatively easy recording of extracellular synaptic responses. Using the classic model, a variety of mechanistically motivated experiments that were not feasible in vivo were performed [5]. It is now understood that the underlying mechanisms of LTP relate to the NMDA (N-methyl-D-aspartate) and AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors [5].…”

“…Using the classic model, a variety of mechanistically motivated experiments that were not feasible in vivo were performed [5]. It is now understood that the underlying mechanisms of LTP relate to the NMDA (N-methyl-D-aspartate) and AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors [5]. The basic properties of LTP, including cooperativity, synaptic specificity and associativity, are found to fit well with Hebb's postulate and can be explained by the biophysical properties of the NMDA receptor that is needed to trigger LTP [6].…”

Morphometric Analysis of Hippocampal and Neocortical Pyramidal Neurons in a Mouse Model of Late Onset Alzheimer’s Disease

“…With respect to electrophysiological properties, there are distinct differences between dorsal and ventral CA1 pyramidal neurons in basic membrane parameters and excitability (e.g., input resistance, resting membrane potential) [15]. Long term potentiation (LTP) is stronger in the dorsal hippocampus, and this is correlated with a higher density of NMDA receptors, higher NMDA-mediated field excitatory postsynaptic potentials [16], and a more effective interaction between NMDA receptors and L-type voltage dependent calcium channels [17]. Furthermore, in the RNA-seq database of gene expression in hippocampal neurons [18], a number of genes in a gene cohort associated with LTP exhibited increased expression in dCA1 neurons relative to vCA1 neurons.…”