Switching between persistent firing and depolarization block in individual rat CA1 pyramidal neurons

Abstract

The hippocampal formation plays a role in mnemonic tasks and epileptic discharges in vivo. In vitro, these functions and malfunctions may relate to persistent firing (PF) and depolarization block (DB), respectively. Pyramidal neurons of the CA1 field have previously been reported to engage in either PF or DB during cholinergic stimulation. However, it is unknown whether these cells constitute disparate populations of neurons. Furthermore, it is unclear which cell‐specific peculiarities may mediate their diverse response properties. However, it has not been shown whether individual CA1 pyramidal neurons can switch between PF and DB states. Here, we used whole cell patch clamp in the current clamp mode on in vitro CA1 pyramidal neurons from acutely sliced rat tissue to test various intrinsic properties which may provoke individual cells to switch between PF and DB. We found that individual cells could switch from PF to DB, in a cholinergic agonist concentration dependent manner and depending on the parameters of stimulation. We also demonstrate involvement of TRPC and potassium channels in this switching. Finally, we report that the probability for DB was more pronounced in the proximal than in the distal half of CA1. These findings offer a potential mechanism for the stronger spatial modulation in proximal, compared to distal CA1, as place field formation was shown to be affected by DB. Taken together, our results suggest that PF and DB are not mutually exclusive response properties of individual neurons. Rather, a cell's response mode depends on a variety of intrinsic properties, and modulation of these properties enables switching between PF and DB.

Intrinsic Morphologic and Physiologic Development of Human Derived Retinal Ganglion Cells In Vitro

“… 21 Depolarization block is generally thought to protect neurons from excessive excitability 53 and may be dependent on presynaptic inputs driving postsynaptic membrane potential and intrinsic factors, including intracellular adenosine triphosphate (ATP) levels, NaV channel activity, and AIS length and NaV channel localization. 21 , 52 , 54 , 55 …”

The CAN‐In network: A biologically inspired model for self‐sustained theta oscillations and memory maintenance in the hippocampus

“…Hence, at higher Cch concentrations a higher fraction of cells had to be excluded because they exhibited depolarization block. Between 15 and 25 Hz appears to lie a cell‐specific persistent firing frequency limit in CA1 pyramidal neurons, beyond which cells tend to show depolarization block (Knauer, ). Unpublished recordings from our laboratory ( n = 19 Long‐Evans rats, 14‐24 days old, 68% males) in the presence of 0.1 ( n = 6), 0.25 ( n = 6), 1 ( n = 5), and 2.5 ( n = 5) μM Cch showed average persistent firing frequencies of 1.5, 0.7, 6.9 and 14.9 Hz, respectively.…”

“…Hence, due the presence of depolarization block 0 (0%), 8 (32%), 29 (42%), and 30 (73%) cells were excluded from the in vitro sample in 1, 5, 10, and 20 mM Cch, respectively, to form the dataset reported here. For further details on the equipment and procedures, see Knauer (2015).…”

Involvement of TRPC4 and 5 Channels in Persistent Firing in Hippocampal CA1 Pyramidal Cells

“…First, we tested ML204, a blocker of the TRPC4 channel which has a higher selectivity for TRPC4 over TRPC3, TRPC5, and TRPC6 [67,74,75]. At the concentration of 10 µM, ML204 mainly blocks TRPC4 channels.…”