Laboratorio de Circuitos Neuronales

The image shows CA2 pyramidal neurons immunostained against PCP4 in magenta and α-Actinin2 in yellow. Cell nuclei are shown in cyan. Image taken by Elena Cid

Proximodistal organization of CA2

The proximodistal axis is considered a major organizational principle of the hippocampus. The CA2 region apparently breaks this rule. We discovered that CA2 is organized around the limit of the mossy fibers (Fernandez-Lamo et al., Cell reports 2019). We found a characteristic molecular gradient within CA2 in the rat and marked proximodistal trends of synaptic activity and phase-locked theta and gamma firing.  Our data suggest that the structure and function of CA2 are distributed along the proximodistal hippocampal axis.

A deep CA1 pyramidal cell recorded and labeled in vivo by Ivan Fernandez-Lamo and processed by Elena Cid

Laminar regionalization of CA1 replay

Recently, we discovered that deep and superficial CA1 pyramidal cells participate differentially during sharp-wave ripples (Valero et al Nat Neu 2015). Using unsupervised clustering of ripple events, we next disclosed a mechanism determining firing selectivity and its distorsion in the epileptic hippocampus (Valero et al. Neuron 2017). Our data support the idea of a strong regionalization of hippocampal function during basic processes underlying memory consolidation, which is a major research line today in our lab.

We found that the fast ripple power spectrum typically leakes into the high-frequency band, due to non-selective out-of-phase firing of CA1 pyramidal cells. Using unsupervised clustering we disclosed variability of fast ripple waveforms

Mechanisms of epileptic fast ripples

Fast ripples are high-frequency oscillations (HFOs) >250 Hz recorded in epileptogenic hippocampal regions. In 2007, we proposed a mechanism by which fast ripples emerge from the pathological desynchronization of neuronal firing (Foffani et al. Neuron 2007). Later in 2010, we developed the out-of-phase firing hypothesis which is now accepted as a major mechanism of pathological HFOs (Ibarz et al. JNeurosc 2010). More recently, we disclosed synaptic mechanisms underlying firing selectivity collapse during fast ripples (Valero et al. Neuron 2017).