The cerebrospinal fluid (CSF) occupies the brain’s ventricles and subarachnoid space and, together with the interstitial fluid (ISF), forms a continuous fluidic network that bathes all cells of the central nervous system. As such, the CSF is well positioned to actively distribute neuromodulators to neural circuits in vivo via volume transmission.
We have recently shown here that replacing artificial CSF (aCSF), routinely used for perfusion of brain slices in vitro, with human CSF (hCSF) powerfully boosts spontaneous firing of CA1, CA3, layer 5 pyramidal neurons as well as of fast spiking- and non-fast spiking interneurons in the rat brain slice. In these experiments, the aCSF was matched to the hCSF with respect to electrolyte and glucose composition. CA1 pyramidal neurons in hCSF display lowered firing thresholds, more depolarized resting membrane potentials and reduced input resistance, mimicking properties of pyramidal neurons recorded in vivo.
The increased excitability of CA1 pyramidal neurons was completely occluded by intracellular application of GTPγS, suggesting that endogenous neuromodulators in hCSF act on G-protein coupled receptors to enhance excitability.
Moreover, replacing aCSF with hCSF induced spontaneous gamma activity in the hippocampal slice that was reversed by washout. Our findings highlight a previously unknown function of the CSF in promoting spontaneous neuronal activity, and may help to explain differences observed in vivo and in vitro.
Björefeldt, Andreasson, Daborg, Riebe, Wasling, Zetterberg and Hanse (2015) Human cerebrospinal fluid increases the excitability of pyramidal neurons in the in vitro brain slice J Physiol 593:231-241
Björefeldt, Wasling, Zetterberg and Hanse (2016) Neuromodulation of fast-spiking and non-fast-spiking hippocampal CA1 interneurons by human cerebrospinal fluid J Physiol 594:937-952
Björefeldt, Roshan, Forsberg, Zetterberg, Hanse and Fisahn (2019) Human cerebrospinal fluid promotes spontaneous gamma oscillations in the hippocampus in vitro Submitted