Abstract
Stimulus-specific adaptation (SSA) is observed in many brain regions in humans and animals. SSA of cortical neurons has been proposed to accumulate through relays in ascending pathways. Here, we examined SSA at the synapse level using whole-cell patch-clamp recordings of primary cultured cortical neurons of the rat. First, we found that cultured neurons had high firing capability with 100-Hz current injection. However, neuron firing started to adapt to repeated electrically activated synaptic inputs at 10 Hz. Next, to activate different dendritic inputs, electrical stimulations were spatially separated. Cultured neurons showed similar SSA properties in the oddball stimulation paradigm compared to those reported in vivo. Single neurons responded preferentially to a deviant stimulus over repeated, standard stimuli considering both synapse-driven spikes and excitatory postsynaptic currents (EPSCs). Compared with two closely placed stimulating electrodes that activated highly overlapping dendritic fields, two separately placed electrodes that activated less overlapping dendritic fields elicited greater SSA. Finally, we used glutamate puffing to directly activate postsynaptic glutamate receptors. Neurons showed SSA to two separately placed puffs repeated at 10 Hz. Compared with EPSCs, GABAa receptor-mediated inhibitory postsynaptic currents showed weaker SSA. Heterogeneity of the synaptic inputs was critical for producing SSA, with glutamate receptor desensitization participating in the process. Our findings suggest that postsynaptic fatigue contributes largely to SSA at low frequencies.
Highlights
Stimulus-specific adaptation (SSA), which is the decline in neuronal response to repeated stimuli but not a novel stimulus, has been demonstrated in humans and animals at multiple spatial and temporal scales [1, 2, 3, 4]
Single action potentials were elicited by a 3-ms intracellular injection of depolarizing current, and 10 sequential action potentials were evoked with inter-stimulus interval (ISI) of 100, 50, 20 or 10 ms to examine firing capabilities at different stimulation frequencies (Fig. 2A)
These findings indicate that membrane excitability was unchanged at stimulation frequencies less than 100 Hz
Summary
Stimulus-specific adaptation (SSA), which is the decline in neuronal response to repeated stimuli but not a novel stimulus, has been demonstrated in humans and animals at multiple spatial and temporal scales [1, 2, 3, 4]. Physiological studies have revealed a commonality of SSA within components of the auditory pathway, with adaptation of cortical neurons resulting from the accumulation of adaptation throughout the ascending auditory pathway [4, 8, 9]. SSA is thought to be generated via intrinsic membrane excitability changes and short-term synaptic depression [1, 8, 17]. Because cultured neurons in vitro form recurrent connections that resemble those in vivo in terms of synaptic and intrinsic properties [17, 18], we investigated SSA using whole-cell patch-clamp recording techniques in cultured networks of rat cortical neurons. To examine the mechanisms of SSA at the synapse level, we employed an oddball stimulation paradigm with spatially separated electrical or chemical stimuli [5]
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