While most CNS neurons respond transiently to synaptic input, neurons in neocortical regions1–3
, and in the hippocampus4,5
, can fire persistently in response to brief stimuli. Persistent firing in these neurons typically lasts for multiple seconds and often is associated with working memory in delayed-response tasks6,7,4
. In nonhuman primates, activity in spatially-tuned “delay neurons” in prefrontal neocortex can predict whether specific stimuli will be correctly recalled. The selective activation of delay neurons during working memory tasks, and the correlation between delay-period discharges and performance6,7,4
, both argue strongly that persistent activity is intimately associated with memory function. While many studies have demonstrated extracellularly-recorded delay period discharges in rodents8
, the cellular mechanism responsible for this behavior has not been established. Persistent firing also has been reported in subcortical brain areas 9,10
, suggesting that this activity may represent a fundamental form of brain dynamics.
The persistent firing mode recorded in single units in vivo
presumably reflects a network up-state since most cortical principal neurons do not fire persistently in response to brief depolarizing steps in vitro
under physiological conditions11,12
. Cell-autonomous persistent firing modes have been reported in several brain regions, but not in cortical neurons typically associated with working memory. Since there have been no previous in vitro
models of cortical up-states that exhibit distinct stimulus-specific persistent activity patterns9
, it has been difficult to determine if intrinsic persistent firing modes are engaged during working memory tasks. Hebb13
, and other researchers14–16
, proposed that reverberating activity circulating through excitatory synaptic networks might mediate persistent discharges in cortical regions. While possible to implement in precisely-tuned computer simulations14,17,18
, the fine control over synaptic strengths required to maintain up-states over seconds in biophysically realistic neurons lacking intrinsic persistent firing modes raises doubts as to the feasibility of this mechanism.
The dentate gyrus is an attractive brain region in which to examine the cellular basis of persistent network activity. The principal neuron in the dentate, the granule cell (GC), forms the first relay in the hippocampal trisynaptic circuit and likely functions to generate transient, sparse representations of complex polysensory input patterns from entorhinal projection neurons. Hilar neurons also exhibit performance-linked persistent firing during cross-sensory modality delayed match-to-sample tests4
, though the cellular mechanism mediating this activity is unknown.
Using acute rat hippocampal slices, we find that perforant path stimulation triggers reproducible patterns of persistent firing in subpopulations of hilar cells that encode information about stimulus identity. Persistent firing in hilar neurons results from prolonged discharges in a recently identified dentate gyrus cell type: the semilunar granule cell (SGC19
). We find that these neurons, located in the inner molecular layer, receive potent glutamatergic input that can trigger plateau potentials maintained by voltage-gated Ca2+
channels. The synaptic interaction between a relatively rare population of broadly-projecting excitatory neurons that generate stable plateau potentials and downstream local circuit networks represents a novel, and potentially generalizable, mechanism that enables transient input to trigger persistent firing in synaptically-coupled networks.