KEY POINTS: The cerebrospinal fluid contains numerous neuromodulators at ambient levels but whether, and how, they affect the activity of central neurons is unknown. This study provides experimental evidence that @entity1 cerebrospinal fluid ( @entity2841 ) increases the excitability of hippocampal and neocortical pyramidal neurons. Hippocampal @entity1399 pyramidal neurons in @entity2841 displayed lowered firing thresholds, depolarized resting membrane potentials and reduced input resistance, mimicking properties of pyramidal neurons recorded in vivo. The excitability-increasing effect of @entity2841 on @entity1399 pyramidal neurons was entirely occluded by intracellular application of GTPyS, suggesting that neuromodulatory effects were mediated by G-protein coupled receptors. These results indicate that the @entity2841 promotes spontaneous excitatory neuronal activity, and may help to explain observed differences in the activity of pyramidal neurons recorded in vivo and in vitro. ABSTRACT: The composition of brain extracellular fluid is shaped by a continuous exchange of substances between the cerebrospinal fluid ( @entity2841 ) and interstitial fluid. The @entity2841 is known to contain a wide range of endogenous neuromodulatory substances, but their collective influence on neuronal activity has been poorly investigated. We show here that replacing artificial @entity2841 (aCSF), routinely used for perfusion of brain slices in vitro, with @entity1 @entity2841 ( @entity2841 ) powerfully boosts spontaneous firing of @entity1399 , @entity1400 and layer 5 pyramidal neurons in the @entity35 brain slice. @entity1399 pyramidal neurons in @entity2841 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 @entity1399 pyramidal neurons was completely occluded by intracellular application of GTPyS, suggesting that endogenous neuromodulators in @entity2841 act on G-protein coupled receptors to enhance excitability. We found no increase in spontaneous inhibitory synaptic transmission by @entity2841 , indicating a differential effect on glutamatergic and GABAergic neurons. Our findings highlight a previously unknown function of the @entity2841 in promoting spontaneous excitatory activity, and may help to explain differences observed in the activity of pyramidal neurons recorded in vivo and in vitro.

XXXX cerebrospinal fluid increases the excitability of pyramidal neurons in the in vitro brain slice.

@entity1 :: ('9606', 'Species') :: ['human'] @entity1400 :: ('761', 'Gene') :: ['CA3'] @entity1399 :: ('759', 'Gene') :: ['CA1'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity2841 :: ('1437', 'Gene') :: ['CSF', 'hCSF']
@entity1 :: (9606,Species) :: ['Human']
