Spike Timing in CA3 Pyramidal Cells During Behavior: Implications for Synaptic Transmission

Abstract

Spike timing is thought to be an important mechanism for transmitting information in the CNS. Recent studies have emphasized millisecond precision in spike timing to allow temporal summation of rapid synaptic signals. However, spike timing over slower time scales could also be important, through mechanisms including activity-dependent synaptic plasticity or temporal summation of slow postsynaptic potentials (PSPs) such as those mediated by kainate receptors. To determine the extent to which these slower mechanisms contribute to information processing, it is first necessary to understand the properties of behaviorally relevant spike timing over this slow time scale. In this study, we examine the activity of CA3 pyramidal cells during the performance of a complex behavioral task in rats. Sustained firing rates vary over a wide range, and the firing rate of a cell is poorly correlated with the behavioral cues to which the cell responds. Nonrandom interactions between successive spikes can last for several seconds, but the nonrandom distribution of interspike intervals (ISIs) can account for the majority of nonrandom multi-spike patterns. During a stimulus, cellular responses are temporally complex, causing a shift in spike timing that favors intermediate ISIs over short and long ISIs. Response discrimination between related stimuli occurs through changes in both response time-course and response intensity. Precise synchrony between cells is limited, but loosely correlated firing between cells is common. This study indicates that spike timing is regulated over long time scales and suggests that slow synaptic mechanisms could play a substantial role in information processing in the CNS.

Distinct classes of pyramidal cells exhibit mutually exclusive firing patterns in hippocampal area CA3b

“…CA3 pyramidal neurons in vivo exhibit a range of firing patterns that can be interpreted as spanning from non-bursting to burst firing (Frerking et al, 2005). It is quite possible that the variability we observed in vitro contributes, at least in part, to that distribution.…”

“…During behavioral tasks the distribution of interspike intervals (ISI) of CA3 pyramidal neurons varies between cells (Frerking et al, 2005) with some neurons exhibiting bimodal distributions suggestive of at least two firing patterns; burst firing which comprises a fast ISI peak and regular, lower-frequency firing corresponding to a longer ISI peak distribution (Frerking et al, 2005).…”

Cysteine String Protein-α Prevents Activity-Dependent Degeneration in GABAergic Synapses

“…More specifically, we have shown that the Syt2-expressing GABAergic synapses (Pang et al, 2006;Fox and Sanes, 2007;Kerr et al, 2008) established by neurons which typically fire action potentials at very high frequencies (ϳ200 Hz) (Ylinen et al, 1995;Csicsvari et al, 1999) are extremely dependent on CSP-␣ to maintain their functional and structural integrity over time, and therefore suffer from progressive degeneration on genetic removal of CSP-␣. In contrast, neighboring glutamatergic synapses from neurons that normally trigger action potentials at a lower frequency (ϳ1 Hz) (Csicsvari et al, 1999;Frerking et al, 2005) do not show signs of presynaptic degeneration in the absence of CSP-␣. These conclusions are based on the following findings: First, using immunofluorescence and electron microscopy, we have demonstrated progressive degeneration of GABAergic synapses both in vitro and in vivo (Fig.…”

Distinguishing linear vs. non-linear integration in CA1 radial oblique dendrites: it’s about time

“…While it is the case that CA3 neurons discharge at very low frequencies on average (1–3 Hz; Csicsvari et al, 2000; Frerking et al, 2005), during the theta rhythm they typically fire bursts of 1–4 spikes (2.4 spikes per burst on average) with inter-spike-intervals (ISIs) ranging from 3 to 7 ms (Ranck, 1973; Tropp-Sneider et al, 2006; Mizuseki et al, 2009). This type of firing pattern is significant since, beyond the opportunity for classical temporal summation afforded by a train of inputs, glutamate binding kinetics lead NMDA conductances to increase substantially in response to brief trains compared to single stimuli (Mainen et al, 1999; Umemiya et al, 1999; Mcallister and Stevens, 2000; Oertner et al, 2002; Nimchinsky et al, 2004; Popescu et al, 2004; Polsky et al, 2009).…”