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  • We next looked at the relationship between the PSTH ratio Epacadostat and the corresponding sinks and sources recorded within the same session to further understand the causes of response differences. To this purpose, we selected those sessions where clear sinks were detected in ML of the DG (28/28) and in SLM of CA1 (15/28). We also included those sessions with clear sources localized around the pyramidal layer of CA1 (14/28). Despite the caveat that extracellular conductances are not necessarily comparable in different sessions/animals, the repeatability of the experimental protocol was high enough to allow us to find significant correlations between CSD and PSTH responses. Specifically, we found correlation between the ML sink at the DG and the corresponding PSTH response at the granular layer, i.e. the stronger the sink (more negative) the more likely to detect DG firing increases (Pearson: r=?0.67, P= 0.0001; Fig. 3G). This suggests that somatosensory stimulation elicits a direct excitatory effect onto DG granule cells, predominantly increasing their firing in association with the current sinks that reflect excitatory dendritic inputs. Quite in contrast, distal SLM sinks appeared unable to modulate CA1 cellular firing (r= 0.39, P= 0.21; Fig. 3H), as previously reported for the direct temporoammonic�CCA1 synapse (Leung et al. 1995). In addition, current sources around the CA1 cell layer negatively correlated with PSTH ratio (r=?0.57; P= 0.0342), from firing increase (PSTH > 1 for weaker SP sources) to firing suppression (PSTH < 1 for stronger SP sources, Fig. 3I). Such a negative correlation would not be expected if the CA1 somatic source were simply a passive return current of the SLM sink. This suggests that somatosensory stimulation Talazoparib cell line elicits a complex modulatory effect onto CA1 pyramidal cells, with firing suppression depending on the strength of the somatic source giving further support to the idea that it might reflect active inhibition. We further looked at cellular responses in the CA1 area and in the DG by using tetrode recordings aimed to isolate single-cell activity from 106 stimulation sessions in 13 rats. In these experiments, we mostly used stimulation of both contralateral paws due to larger stimulation artifacts when using whisker stimuli. Using semi-automatic and supervised cluster algorithms we grouped units according to amplitude variations of the waveform in different channels and standard parameters of spike width, asymmetry and firing dynamics. CA1 and DG units were classified as interneurons depending on their short trough-to-peak duration and a waveform asymmetry index (Fig. 4A and B), together with information about their spontaneous firing pattern (Fig. 5Aa�CEa). Cells not classified as interneurons were subsequently examined to see whether they match classification criteria for principal cells (i.e. pyramidal cells in CA1 or granule cells in the DG; see Methods).

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