The rodent primary somatosensory cortex is spontaneously active in the form of locally synchronous membrane depolarizations (UP states) separated by quiescent hyperpolarized periods (DOWN states) both under anesthesia and during quiet wakefulness. In vivo whole-cell recordings and tetrode unit recordings were combined with voltage-sensitive dye imaging to analyze the relationship of the activity of individual pyramidal neurons in layer 2͞3 to the ensemble spatiotemporal dynamics of the spontaneous depolarizations. These were either brief and localized to an area of a barrel column or occurred as propagating waves dependent on local glutamatergic synaptic transmission in layer 2͞3. Spontaneous activity inhibited the sensory responses evoked by whisker deflection, accounting almost entirely for the large trial-to-trial variability of sensory-evoked postsynaptic potentials and action potentials. Subthreshold sensory synaptic responses evoked while a cortical area was spontaneously depolarized were smaller, briefer and spatially more confined. Surprisingly, whisker deflections evoked fewer action potentials during the spontaneous depolarizations despite neurons being closer to threshold. The ongoing spontaneous activity thus regulates the amplitude and the time-dependent spread of the sensory response in layer 2͞3 barrel cortex.T he neocortex is spontaneously active. Neocortical neurons in vivo exhibit spontaneous subthreshold membrane potential changes, which can evoke spontaneous action potentials (APs). Such spontaneous activity is not only found in association cortex but is also evident in primary sensory areas. Previous studies have shown that both during slow wave sleep and during anesthesia, the brain state is characterized by low frequency, large amplitude spontaneous membrane potential changes (1-3). Dual intracellular recordings have demonstrated that such spontaneous activity can occur synchronously in nearby neurons (4). Voltage-sensitive dye (VSD) imaging has shown complex patterns of spatiotemporal dynamics of the ensemble spontaneous activity (5-7). The nature of this spontaneous activity and how it interacts with sensory responses is poorly understood.To investigate the relationship between sub-and suprathreshold membrane potential changes of individual neurons in layer 2͞3 and the surrounding network, we combined whole-cell (WC) recordings, VSD imaging, and tetrode recordings for in vivo measurements in rodent barrel cortex. Surprisingly, unlike in the anesthetized cat where spontaneous depolarization enhanced responses (6, 8, 9), here we find that both sensory-evoked postsynaptic potentials (PSPs) and sensory-evoked APs are suppressed by ongoing spontaneous activity. This spontaneous activity occurs as both brief localized depolarizations and propagating waves of glutamatergic excitation in layer 2͞3. MethodsSurgical Procedures. Wistar rats or mice C57BL6 aged P21-P35 were anesthetized with urethane (1.5-2 g/kg), ketamine (100 mg/kg)͞xylazine (20 mg/kg), or halothane (1.5-2%). Paw withdrawal, whisk...

We propose a novel parameter, namely, the skewness, or asymmetry, of the shape of a receptive field to characterize two properties of hippocampal place fields. First, a majority of hippocampal receptive fields on linear tracks are negatively skewed, such that during a single pass the firing rate is low as the rat enters the field but high as it exits. Second, while the place fields are symmetric at the beginning of a session, they become highly asymmetric with experience. Further experiments suggest that these results are likely to arise due to synaptic plasticity during behavior. Using a purely feed forward neural network model, we show that following repeated directional activation, NMDA-dependent long-term potentiation/long-term depotentiation (LTP/LTD) could result in an experience-dependent asymmetrization of receptive fields.

Theories of sequence learning based on temporally asymmetric, Hebbian long-term potentiation predict that during route learning the spatial firing distributions of hippocampal neurons should enlarge in a direction opposite to the animal's movement. On a route AB, increased synaptic drive from cells representing A would cause cells representing B to fire earlier and more robustly. These effects appeared within a few laps in rats running on closed tracks. This provides indirect evidence for Hebbian synaptic plasticity and a functional explanation for why place cells become directionally selective during route following, namely, to preserve the synaptic asymmetry necessary to encode the sequence direction.Rat hippocampal neurons fire in a spatially selective fashion (1). Recently it was proposed that the hippocampus might store route information through Hebbian (2) asymmetric strengthening of synapses between cells with overlapping place fields on a route (3-7). A prediction of this asymmetric synaptic enhancement was an expansion of place fields and a shift in their centers of mass in a direction opposite to the direction of the route. The present study was designed to investigate whether the predicted asymmetric place field expansion indeed occurs.Evidence for the reactivation of sequence information has been demonstrated in hippocampal neuronal ensembles during slow-wave sleep following repetitive, unidirectional traversal of a closed route (8). There is also abundant evidence, from experiments conducted under conditions of artificial, electrical stimulation, that a potential mechanism for experience-dependent synaptic change, with the necessary associative (9) and asymmetric properties, exists (10-12). The observation of the predicted, asymmetric expansion of place fields would provide strong indirect evidence that such processes are actually at work during the registration of sequences of spatial experience. MATERIALS AND METHODSSeven Fischer-344 rats were pretrained to run for food reinforcement at fixed locations on triangular (60 cm per side) or rectangular (66 cm ϫ 37 cm) tracks (each 6 cm wide) situated in a moderately illuminated room with fixed landmarks. Populations of hippocampal CA1 pyramidal cells were simultaneously recorded using multiple ''tetrodes'' as the rats performed the task, using methods described previously (13). The position and orientation of two head-mounted diode arrays (separated by 15 cm) was measured by a video camera (0.41 cm per pixel sampled at 20 Hz). Data were analyzed (i) from one session each from seven rats, in which they ran unidirectionally around the apparatus, and (ii) from three additional sessions in two of the rats, in which they followed the same route on consecutive days. Data were also analyzed from four sessions in three animals that ran on a novel track immediately after running on the familiar one.Because place-specific discharge appears primarily during movement, and because the rats stopped at the food locations, place fields around food locations we...