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

Sublayer organization 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.

Using unsupervised clustering we disclosed variability of fast ripple waveforms. 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.

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, using unsupervised learning we disclosed synaptic mechanisms underlying firing selectivity collapse during fast ripples (Valero et al. Neuron 2017).