Sustained increase of spontaneous input and spike transfer in the CA3-CA1 pathway following long-term potentiation in vivo

Abstract

Long-term potentiation (LTP) is commonly used to study synaptic plasticity but the associated changes in the spontaneous activity of individual neurons or the computational properties of neural networks in vivo remain largely unclear. The multisynaptic origin of spontaneous spikes makes it difficult to estimate the impact of a particular potentiated input. Accordingly, we adopted an approach that isolates pathway-specific postsynaptic activity from raw local field potentials (LFPs) in the rat hippocampus in order to study the effects of LTP on ongoing spike transfer between cell pairs in the CA3-CA1 pathway. CA1 Schaffer-specific LFPs elicited by spontaneous clustered firing of CA3 pyramidal cells involved a regular succession of elementary micro-field-EPSPs (gamma-frequency) that fired spikes in CA1 units. LTP increased the amplitude but not the frequency of these ongoing excitatory quanta. Also, the proportion of Schaffer-driven spikes in both CA1 pyramidal cells and interneurons increased in a cell-specific manner only in previously connected CA3-CA1 cell pairs, i.e., when the CA3 pyramidal cell had shown pre-LTP significant correlation with firing of a CA1 unit and potentiated spike-triggered average (STA) of Schaffer LFPs following LTP. Moreover, LTP produced subtle reorganization of presynaptic CA3 cell assemblies. These findings show effective enhancement of pathway-specific ongoing activity which leads to increased spike transfer in potentiated segments of a network. They indicate that plastic phenomena induced by external protocols may intensify spontaneous information flow across specific channels as proposed in transsynaptic propagation of plasticity and synfire chain hypotheses that may be the substrate for different types of memory involving multiple brain structures.

Entorhinal-CA3 Dual-Input Control of Spike Timing in the Hippocampus by Theta-Gamma Coupling

“…Applied to linear profiles of LFPs it can separate physiologically meaningful sources that can be attributed to known anatomical pathways, as has been demonstrated for the CA1, CA3 and dentate regions of the rat hippocampus (Benito et al, 2014; Fernandez-Ruiz et al, 2012a; Fernandez-Ruiz et al, 2012b; Fernandez-Ruiz et al, 2013). …”

Mitochondrial support of persistent presynaptic vesicle mobilization with age-dependent synaptic growth after LTP

“…Enhanced mobilization of either pool could result in a decrease in presynaptic vesicles. Following induction of LTP, both evoked vesicle release probability (Enoki et al, 2009; Stanton et al, 2005; Zakharenko et al, 2001) and spontaneous miniature excitatory synaptic potentials (Malgaroli and Tsien, 1992; 1995; Manabe et al, 1992; Fernández-Ruiz et al, 2012) have been reported to be increased. Since the potentiation of the (evoked) fEPSP plateaued by 5 min, but TBS-related vesicle mobilization was only detected after 30 min, the persistent enhancement of vesicle mobilization seems more likely to have involved spontaneously released vesicles.…”

Cytoarchitectonic and Dynamic Origins of Giant Positive Local Field Potentials in the Dentate Gyrus

“…Accordingly, the size and geometry of the blocks of current represent the physical extension of the synchronously activated GCs, i.e., the portion of the GC population that elicits postsynaptic currents upon coherent activation of a group of axons from homologous afferent units (Benito et al, 2013). The FEM approach is widely used in magnetoencephalography and scalp electroencephalogram (EEG; Chen and Mogul, 2009;Salvador et al, 2011;Thielscher et al, 2011), although to the best of our knowledge it has not previously been used in the study of LFPs where the modeling approaches included realistic connectivity and/or membrane electrogenesis (Pauluis et al, 1999;Varona et al, 2000;Ló pez-Aguado et al, 2002;Lindén et al, 2011;Makarova et al, 2011;Ho et al, 2012).…”

“…For instance, because the spatial coherence of LFPs may be due to macroscopic blending of nonoverlapping synaptic territories of functionally coupled neurons (e.g., interneuron networks), it is possible that statedependent modulation of network coupling disproportionately reduces the visualization of their associated LFPs with respect to individual firing rates, as demonstrated here by reducing the size of the activation strips. These observations are relevant to the study of the cellular mechanisms underlying LFP phenomena including dentate spikes, sharp waves, ripples, and field oscillations, which can appear at different hippocampal loci and with varying degrees of spatial coverage (Bragin et al, 1995a,b;Csicsvari et al, 2000;Bibbig et al, 2007;Reichinnek et al, 2010).…”