Compared with other areas of the forebrain, the function of insular cortex is poorly understood. This study examined the unisensory and multisensory function of the rat insula using high-resolution, whole-hemisphere, epipial evoked potential mapping. We found the posterior insula to contain distinct auditory and somatotopically organized somatosensory fields with an interposed and overlapping region capable of integrating these sensory modalities. Unisensory and multisensory responses were uninfluenced by complete lesioning of primary and secondary auditory and somatosensory cortices, suggesting a high degree of parallel afferent input from the thalamus. In light of the established connections of the posterior insula with the amygdala, we propose that integration of auditory and somatosensory modalities reported here may play a role in auditory fear conditioning.

Oscillatory activity in excess of several hundred hertz has been observed in somatosensory evoked potentials (SEP) recorded in both humans and animals and is attracting increasing interest regarding its role in brain function. Currently, however, little is known about the cellular events underlying these oscillations. The present study employed simultaneous in-vivo intracellular and epipial field-potential recording to investigate the cellular correlates of fast oscillations in rat somatosensory cortex evoked by vibrissa stimulation. Two distinct types of fast oscillations were observed, here termed "fast oscillations" (FO) (200-400 Hz) and "very fast oscillations" (VFO) (400-600 Hz). FO coincided with the earliest slow-wave components of the SEP whereas VFO typically were later and of smaller amplitude. Regular spiking (RS) cells exhibited vibrissa-evoked responses associated with one or both types of fast oscillations and consisted of combinations of spike and/or subthreshold events that, when superimposed across trials, clustered at latencies separated by successive cycles of FO or VFO activity, or a combination of both. Fast spiking (FS) cells responded to vibrissae stimulation with bursts of action potentials that closely approximated the periodicity of the surface VFO. No cells were encountered that produced action potential bursts related to FO activity in an analogous fashion. We propose that fast oscillations define preferred latencies for action potential generation in cortical RS cells, with VFO generated by inhibitory interneurons and FO reflecting both sequential and recurrent activity of stations in the cortical lamina.

Brain glial cells, five times more prevalent than neurons, have recently received attention for their potential involvement in epileptic seizures. Microglia and astrocytes, associated with inflammatory innate immune responses, are responsible for surveillance of brain damage that frequently results in seizures. Thus, an intriguing suggestion has been put forward that seizures may be facilitated and perhaps triggered by brain immune responses. Indeed, recent evidence strongly implicates innate immune responses in lowering seizure threshold in experimental models of epilepsy, yet, there is no proof that they can play an independent role in initiating seizures in vivo. Here, we show that cortical innate immune responses alone produce profound increases of brain excitability resulting in focal seizures. We found that cortical application of lipopolysaccharide, binding to toll-like receptor 4 (TLR4), triples evoked field potential amplitudes and produces focal epileptiform discharges. These effects are prevented by pre-application of interleukin-1 receptor antagonist. Our results demonstrate how the innate immune response may participate in acute seizures, increasing neuronal excitability through interleukin-1 release in response to TLR4 detection of the danger signals associated with infections of the central nervous system and with brain injury. These results suggest an important role of innate immunity in epileptogenesis and focus on glial inhibition, through pharmacological blockade of TLR4 and the pro-inflammatory mediators released by activated glia, in the study and treatment of seizure disorders in humans.

A 64-channel electrode array was used to study the spatial and temporal characteristics of fast (>200 Hz) electrical oscillations recorded from the surface of rat cortex in both awake and anesthetized animals. Transient vibrissal displacements were effective in evoking oscillatory responses in the vibrissa/barrel field and were tightly time-locked to stimulus onset, coinciding with the earliest temporal components of the coincident slow-wave response. Vibrissa-evoked fast oscillations exhibited modality specificity and were earliest and of largest amplitude over the cortical barrel, which corresponded to the vibrissa stimulated, spreading to sequentially engage neighboring barrels over subsequent oscillatory cycles. The response was enhanced after paired-vibrissal stimulation and was sensitive to time delays between movement of separate vibrissae. These data suggest that spatiotemporal interactions between fast oscillatory bursts in the barrel field may play a role in rapidly integrating information from the vibrissal array during the earliest cortical response to somatosensory stimulation.

1. A 16-channel electrode array was used to record simultaneously extracellular laminar field potentials evoked by displacement of contralateral vibrissa from vibrissa/barrel cortex in five rats. Current source-density (CSD) analysis combined with principal component analysis (PCA) was used to determine the time course of laminar-specific transmembrane currents during the evoked response. 2. The potential complex consisted of biphasic fast components followed by long-lasting slow waves. It began with activity in supragranular cells consisting of a source in layers I-II and a sink in layers IV-V; this was followed by activation of the infragranular cells with a paired sink and source in layers I-IV and V-VI, respectively. The slow-wave sequences also began in the supragranular cells followed by infragranular neurons. 3. We propose that the fast components reflect sequential intralaminar depolarization processes, and the slow waves, hyper- or repolarization processes. These results suggest that a basic neuronal circuit, consisting of sequential activation of the supragranular and then the infragranular pyramidal cells, gives rise to the field potentials evoked by physiological stimulation. This is consistent with our previous studies of direct cortical responses (DCR) and pathological discharges of the penicillin focus.

BACKGROUND Safety signals exert a powerful buffering effect when provided during exposure to uncontrollable stressors. We evaluated the role of the sensory insular cortex (Si) and the extend amygdala in this “safety signal effect.” METHODS Rats were implanted with microinjection cannula, exposed to inescapable tailshocks either with or without a safety signal and later tested for anxiety-like behavior or neuronal Fos expression. RESULTS Exposure to the uncontrollable stressor reduced later social exploration, but not when safety signals were present. Temporary inhibition of Si during stressor exposure, but not during later behavioral testing, blocked the safety signal effect on social exploration. The stressor induced Fos in all regions of the amygdala, but safety signals significantly reduced the number of Fos immunoreactive cells in the basolateral amygdala and ventrolateral region of the bed nucleus of the stria terminalis (BNSTlv). Inhibition of BNSTlv neuronal activity during uncontrollable stressor exposure prevented the later reduction in social exploration. Finally, safety signals reduced the time spent freezing during uncontrollable stress. CONCLUSIONS These data suggest that safety signals inhibit the neural fear or anxiety response that normally occurs during uncontrollable stressors and that inhibition of the BNSTlv is sufficient to prevent later anxiety. These data lend support to a growing body of evidence that chronic fear is mediated in the basolateral amygdala and BNSTlv and that environmental factors that modulate fear during stress will alter the long-term consequences of the stressor.

Safety signals are learned cues that predict stress-free periods whereas behavioral control is the ability to modify a stressor by behavioral actions. Both serve to attenuate the effects of stressors such as uncontrollable shocks. Internal and external cues produced by a controlling behavior are followed by a stressor-free interval, and so it is possible that safety learning is fundamental to the effect of control. If this is the case then behavioral control and safety should recruit the same neural machinery. Interestingly, safety signals that prevented a behavioral outcome of stressor exposure that is also blocked by control (reduced social exploration) failed to inhibit activity in the dorsal raphé nucleus or use the ventromedial prefrontal cortex, the mechanisms by which behavioral control operates. However, bilateral lesions to a region of posterior insular cortex, termed the "sensory insula," prevented the effect of safety but not of behavioral control, providing a double-dissociation. These results indicate that stressor-modulators can recruit distinct neural circuitry and imply a critical role of the sensory insula in safety learning.

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