Activation of adult rat CNS endothelial cells by opioid-induced toll-like receptor 4 (TLR4) signaling induces proinflammatory, biochemical, morphological, and behavioral sequelae.

CNS immune signaling contributes to deleterious opioid effects including hyperalgesia, tolerance, reward, and dependence/withdrawal. Such effects are mediated by opioid signaling at toll-like receptor 4 (TLR4), presumptively of glial origin. Whether CNS endothelial cells express TLR4 is controversial. If so, they would be well positioned for activation by blood-borne opioids, contributing to opioid-induced pro-inflammatory responses. These studies examined adult primary rat CNS endothelial cell responses to (-)-morphine or its mu opioid receptor (MOR)-inactive metabolite morphine-3-glucuronide (M3G), both known TLR4 agonists. We demonstrate that adult rat CNS endothelial cells express functional TLR4. M3G activated nuclear factor kappaB (NF-κB), increased tumor necrosis factor-α (TNFα) and cyclooxygenase-2 (COX2) mRNAs, and released prostaglandin E2 (PGE2) from these cells. (-)-Morphine-induced upregulation of TNFα mRNA and PGE2 release were unmasked by pre-treatment with nalmefene, a MOR antagonist without TLR4 activity (unlike CTAP, shown to have both MOR- and TLR4-activity), suggestive of an interplay between MOR and TLR4 co-activation by (-)-morphine. In support, MOR-dependent Protein Kinase A (PKA) opposed TLR4 signaling, as PKA inhibition (H-89) also unmasked (-)-morphine-induced TNFα and COX2 mRNA upregulation. Intrathecal injection of CNS endothelial cells, stimulated in vitro with M3G, produced TLR4-dependent tactile allodynia. Further, cortical suffusion with M3G in vivo induced TLR4-dependent vasodilation. Finally, endothelial cell TLR4 activation by lipopolysaccharide and/or M3G was blocked by the glial inhibitors AV1013 and propentofylline, demonstrating endothelial cells as a new target of such drugs. These data indicate that (-)-morphine and M3G can activate CNS endothelial cells via TLR4, inducing proinflammatory, biochemical, morphological, and behavioral sequelae. CNS endothelial cells may have previously unanticipated roles in opioid-induced effects, in phenomena blocked by presumptive glial inhibitors, as well as TLR4-mediated phenomena more broadly.

Cellular mechanisms of thalamically evoked gamma oscillations in auditory cortex.

The purpose of this study was to clarify the neurogenesis of thalamically evoked gamma frequency (approximately 40 Hz) oscillations in auditory cortex by comparing simultaneously recorded extracellular and intracellular responses elicited with electrical stimulation of the posterior intralaminar nucleus of the thalamus (PIL). The focus of evoked gamma activity was located between primary and secondary auditory cortex using a 64-channel epipial electrode array, and all subsequent intracellular recordings and single-electrode field potential recordings were made at this location. These data indicate that PIL stimulation evokes gamma oscillations in auditory cortex by tonically depolarizing pyramidal cells in the supra- and infragranular layers. No cells revealed endogenous membrane properties capable of producing activity in the gamma frequency band when depolarized individually with injected current, but all displayed both sub- and supra-threshold responses time-locked to extracellular fast oscillations when the population was depolarized by PIL stimulation. We propose that cortical gamma oscillations may be produced and propagated intracortically by network interactions among large groups of neurons when mutually excited by modulatory input from the intralaminar thalamus and that these oscillations do not require specialized pacemaker cells for their neurogenesis.

NeuroD-null mice are deaf due to a severe loss of the inner ear sensory neurons during development.

A key factor in the genetically programmed development of the nervous system is the death of massive numbers of neurons. Therefore, genetic mechanisms governing cell survival are of fundamental importance to developmental neuroscience. We report that inner ear sensory neurons are dependent on a basic helix-loop-helix transcription factor called NeuroD for survival during differentiation. Mice lacking NeuroD protein exhibit no auditory evoked potentials, reflecting a profound deafness. DiI fiber staining, immunostaining and cell death assays reveal that the deafness is due to the failure of inner ear sensory neuron survival during development. The affected inner ear sensory neurons fail to express neurotrophin receptors, TrkB and TrkC, suggesting that the ability of NeuroD to support neuronal survival may be directly mediated through regulation of responsiveness to the neurotrophins.

Intracellular correlates of fast (>200 Hz) electrical oscillations in rat somatosensory cortex.

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.

Spatiotemporal organization of fast (>200 Hz) electrical oscillations in rat Vibrissa/Barrel cortex.

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.

Three-dimensional analysis of spontaneous and thalamically evoked gamma oscillations in auditory cortex.

The purpose of this study was to investigate interactions among laminar cell populations producing spontaneous and evoked high-frequency (approximately 40 Hz) gamma oscillations in auditory cortex. Electrocortical oscillations were recorded using a 64-channel epipial electrode array and a 16-channel linear laminar electrode array while electrical stimulation was delivered to the posterior intralaminar (PIL) nucleus. Spontaneous gamma oscillations, and those evoked by PIL stimulation, are confined to a location overlapping primary and secondary auditory cortex. Current source-density and principal components analysis of laminar recordings at this site indicate that the auditory evoked potential (AEP) complex is characterized by a stereotyped asynchronous activation of supra- and infragranular cell populations. Similar analysis of spontaneous and evoked gamma waves reveals a close spatiotemporal similarity to the laminar AEP, indicating rhythmic interactions between supra- and infragranular cell groups during these oscillatory phenomena. We conclude that neural circuit interactions producing the laminar AEP onset in auditory cortex are the same as those generating evoked and spontaneous gamma oscillations.

Focal stimulation of the thalamic reticular nucleus induces focal gamma waves in cortex.

Electrical stimulation of the thalamic reticular nucleus (TRN; 0.5-s trains of 500-Hz 0.5-ms pulses at 5-10 microA) evokes focal oscillations of cortical electrical potentials in the gamma frequency band ( approximately 35-55 Hz). These evoked oscillations are specific to either the somatosensory or auditory cortex and to subregions of the cortical receptotopic map, depending on what part of the TRN is stimulated. Focal stimulation of the internal capsule, however, evokes focal slow potentials, without gamma activity. Our results suggest that the TRN's role extends beyond that of general cortical arousal to include specific modality and submodality activation of the forebrain.

Sensory-evoked high-frequency (gamma-band) oscillating potentials in somatosensory cortex of the unanesthetized rat.

A 64-channel epipial electrode array was used to investigate high-frequency (gamma-band) oscillations in somatosensory cortex of the unanesthetized and unrestrained rat. Oscillations were evoked by manual stimulation of the vibrissae and mystacial pad. Stimulation of the contralateral vibrissae resulted in a significant increase in gamma-power during 128-ms epochs taken just following stimulus onset compared to the prestimulus baseline. Stimulation of the ipsilateral vibrissae was completely ineffective in evoking gamma-oscillations in any animals. Sensory evoked gamma-oscillations were constrained to primary (SI) and secondary (SII) somatosensory cortex. When averaged to an arbitrary reference of peak times in one of the channels, these oscillations exhibited a systematic temporal organization, propagating from the rostral portion of SI to the barrel field proper, and finally to SII. These spatiotemporal characteristics were probably produced by intracortical pathways within rodent somatosensory cortex. The rostrocaudal propagation of gamma-oscillations within the barrel field may also reflect whisking patterns observed when the vibrissae are used as a sensory array, suggesting that synchronized gamma-oscillations may play a role in assembling punctate afferent information provided by the vibrissae into a coherent representation of a somatosensory stimulus.

Subcortical modulation of high-frequency (gamma band) oscillating potentials in auditory cortex.

The purpose of this study was to use depth electrical stimulation and retrograde horseradish peroxidase (HRP) labeling to determine what role certain subcortical nuclei play in the neurogenesis of high-frequency gamma (approximately 40 Hz) oscillations in rat auditory cortex. Evoked and spontaneous electrocortical oscillations were recorded with the use of a high-spatial-resolution multichannel epipial electrode array while electrical stimulation was delivered to the posterior intralaminar (PIL) region of the ventral acoustic thalamus and to the centrolateral nucleus (CL) and the nucleus basalis (NB), which have been previously implicated in the production of cortical gamma oscillations. PIL stimulation consistently evoked gamma oscillations confined to a location between primary and secondary auditory cortex, corresponding to the region where spontaneous gamma oscillations were also recorded. Stimulation of the CL and NB did not evoke gamma oscillations in auditory cortex. HRP placed in the cortical focus of evoked gamma oscillations labeled cell bodies in the PIL, and in more lateral regions of the ventral acoustic thalamus, which on subsequent stimulation also evoked gamma oscillations in auditory cortex. No cells were labeled in either the CL or NB. These results indicate that the PIL and the lateral regions of ventral acoustic thalamus provide anatomically distinct input to auditory cortex and may play an exclusive and modality-specific role in modulating gamma oscillations in the auditory system.

Thalamic modulation of high-frequency oscillating potentials in auditory cortex.

Perhaps the most widely recognized but least understood electrophysiological activity of the cerebral cortex is its characteristic electrical oscillations. Recently, there have been efforts to understand the mechanisms underlying high-frequency gamma oscillations(approximately 40 Hz) because they may coordinate sensory processing between populations of cortical cells. High-resolution cortical recordings show the gamma oscillations are constrained to sensory cortex, that they occur independently in auditory and somatosensory cortex, and that they are phase-locked between primary and secondary sensory cortex. As yet, the mechanism of their neurogenesis is unknown. Whereas cortical neurons can produce gamma oscillations without subcortical input, they may also be modulated by the thalamus and basal forebrain. Here we report that the neural generator of gamma oscillations in auditory cortex seems to be intracortical, serving to synchronize interactions between the primary and secondary areas. The acoustic thalamus directly modulates these oscillations, which are inhibited by stimulation of the dorsal and ventral divisions of the medial geniculate nucleus (MGd and MGv) and evoked by stimulation of the adjacent posterior intralaminar nucleus (PIL).

Inter- and intra-hemispheric spatiotemporal organization of spontaneous electrocortical oscillations.

1. Two 64-channel epipial electrode arrays were positioned on homologous locations of the right and left hemisphere, covering most of primary and secondary auditory and somatosensory cortex in eight lightly anesthetized rats. Array placement was verified with the use of cytochrome oxidase histochemistry. 2. Middle-latency auditory and somatosensory evoked potentials (MAEPs and MSEPs, respectively) and spontaneous oscillations in the frequency range of 20-40 Hz (gamma oscillations) were recorded and found to be spatially constrained to regions of granular cortex, suggesting that both phenomena are closely associated with sensory information processing. 3. The MAEP and MSEP consisted of an initial biphasic sharp wave in primary auditory and somatosensory cortex, respectively, and a similar biphasic sharp wave occurred approximately 4-8 ms later in secondary sensory cortex of the given modality. Averaged gamma oscillations also revealed asynchronous activation of sensory cortex, but with a shorter 2-ms delay between oscillations in primary and secondary regions. Although the long latency shift of the MAEP and MSEP may be due in part to asynchronous activation of parallel thalamocortical projections to primary and secondary sensory cortex, the much shorter shift of gamma oscillations in a given modality is consistent with intracortical coupling of these regions. 4. Gamma oscillations occurred independently in auditory and somatosensory cortex within a given hemisphere. Furthermore, time series averaging revealed that there was no phase-locking of oscillations between the sensory modalities. 5. Gamma oscillations were loosely coupled between hemispheres; oscillations occurring in auditory or somatosensory cortex of one hemisphere were often associated with lower-amplitude oscillations in homologous contralateral sensory cortex. Yet, the fact that time series averaging revealed no interhemispheric phase-locking suggests that the corpus callosum may not coordinate the bilateral gamma oscillations, and that a thalamic modulatory influence may be involved.

The effects of subcortical lesions on evoked potentials and spontaneous high frequency (gamma-band) oscillating potentials in rat auditory cortex.

Functional subdivisions of auditory cortex in the rat were identified based on the distribution of temporal components of the mid-latency auditory evoked potential (MAEP) recorded with a multichannel epipial electrode array. Spontaneous data collected from the same location exhibited spindle-shaped bursts of oscillations in the gamma-band (20-40 Hz) whose location and spatial distribution were similar to that of the MAEP complex in that the bursts were localized to primary and secondary auditory cortex, the principle targets of thalamocortical projections. This suggested that the neural generators of these electrophysiological events may be similar. However, ablation of the medial geniculate nucleus (MG) of the thalamus revealed that while this nucleus is required for the generation of MAEPs, it is not required for the generation of spontaneous gamma-band oscillations. Ablation of subcortical cholinergic nuclei revealed that cholinergic input via the thalamus or the basal forebrain is not necessary for the generation of either MAEPs or spontaneous gamma-band oscillations recorded in this study. These results indicated that there may be networks of cells in sensory cortical areas endowed with an intrinsic capacity to oscillate independently of sensory or cholinergic input, but that may be modulated by this input.

High frequency (gamma-band) oscillating potentials in rat somatosensory and auditory cortex.

An 8 x 8 multichannel electrode array was used to record epipial field potentials, spontaneous gamma oscillations, and the interaction between single trial evoked potentials and ongoing gamma activity in rat somatosensory and auditory Cortex. Array placement over both these cortical regions was verified using cytochrome oxidase histochemistry. Replicating earlier findings, the epipial middle latency auditory and somatosensory evoked potentials (MAEP and MSEP, respectively) consisted of a stereotyped pattern of activation characterized by a spatially confined biphasic sharp wave followed by more diffuse slow wave components whose areal distribution adhered closely to established boundaries of primary and secondary sensory cortex. Spontaneous gamma activity, while exhibiting far more spatiotemporal variation, was also centered on primary and secondary sensory cortex and was significantly attenuated at intercalated dysgranular regions. A modality specificity of gamma activity was also demonstrated in the present study, where spindles occurred independently in auditory and somatosensory cortex. Furthermore, following presentation of a single click or vibrissal displacement, spontaneous gamma activity was suppressed and subsequently enhanced only in the modality stimulated. We conclude that in the lightly anesthetized rodent, spontaneous gamma oscillations are not a global neocortical phenomena, but are instead restricted to the same areas of sensory cortex participating in evoked potentials. However, unlike the MAEP and MSEP which are dominated by systematic activation of parallel thalamocortical projections, the marked spatiotemporal variability of gamma spindles suggests a more complex neurogenesis, probably including dominant contributions from intracortical neural circuitry.

Comparison of evoked potentials and high-frequency (gamma-band) oscillating potentials in rat auditory cortex.

1. Transient and steady-state (40 Hz) evoked potentials, as well as spontaneous and click-evoked gamma-band oscillations, were recorded from 15 lightly anesthetized rats using an 8 x 8 electrode epipial array covering auditory cortex and adjacent areas to determine and compare the spatiotemporal distributions of these four phenomena. 2. The transient evoked response replicated earlier findings in our laboratory, consisting of an initial biphasic sharp wave in area 41, a similar but delayed biphasic sharp wave in area 36, and more widely distributed slow-wave components. Spatiotemporal analysis supported a model of parallel and asynchronous activation of distinct groups of thalamocortical projections underlying the neurogenesis of these temporal components of the middle-latency auditory evoked potential (MAEP) complex. 3. The 40-Hz response to click trains was superimposed on a steady potential shift (SP), both of which were localized within primary auditory cortex. Epipial distributions of the SP were similar to those of the shortest-latency negative peak in area 41 recorded in the same animals, suggesting similar neural generators. The 40-Hz response was more focal and dissimilar from the SP and any other temporal components of the MAEP complex, suggesting that a unique subpopulation of cells underlies its neurogenesis. 4. Spontaneous gamma-band activity, as assessed by power spectrum analysis, was localized to primary and secondary auditory cortex but had a variable distribution between rats that did not conform to the cytoarchitectonic boundaries within subdivisions of this region. Digital movies computed for individual bursts of gamma-activity indicated a high degree of spatiotemporal variability within and between bursts. 5. Single-trial spectral analysis of click responses indicated an inhibition of gamma-band oscillations during most of the MAEP complex, with subsequent enhanced gamma-activity during the 300- to 350-ms slow-wave component that outlasted the MAEP by approximately 500 ms. The epipial distributions of prestimulus and enhanced poststimulus gamma-oscillations were the same. In contrast to the 40-Hz response to click trains, phase-locking of gamma-oscillations by the single click stimulus was not observed. 6. These results suggest that both the MAEP complex and the steady-state 40-Hz response with its associated SP are highly stereotyped in lightly anesthetized rodent cortex. Their spatiotemporal distributions are probably determined in large part by asynchronous activation of parallel thalamocortical projection systems. Our data suggest no direct link between either the MAEP or the steady-state 40-Hz response to spontaneous or evoked gamma-band oscillations in auditory cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

The spatiotemporal organization of auditory, visual, and auditory-visual evoked potentials in rat cortex.

Four placements of an 8 x 8 channel microelectrode array were used to map auditory, visual, and combined auditory-visual evoked potentials (AEP, VEP, AVEP) from a total of 256 electrode sites over a 7 x 7 mm2 area including most of somatosensory, auditory, and visual cortex in the right hemisphere of the rat. The unimodal AEP and VEP consisted of an archetypal response sequence representing a systematic spatial and temporal activation of primary and secondary sensory cortex. Spatiotemporal analysis of these waveforms indicated that they could be decomposed into a small number of spatial and temporal components; components that are related to patterns of specific and non-specific thalamocortical projections connecting the auditory and visual nuclei of the thalamus with primary and secondary auditory and visual cortex. These data suggest that the AEP and VEP complex are the cortical reflection of asynchronous activation of parallel thalamocortical projection systems. The areal distribution of the AEP and VEP also overlapped, primarily in secondary auditory and visual cortex, indicating that these regions contain populations of cells responding to either modality. Polymodal auditory-visual stimulation resulted in unique activation of two isolated populations of neurons positioned in secondary auditory and secondary visual cortex which were revealed by difference waveforms, computed by subtracting the sum of the AEP and VEP from the AVEP complex. Retrograde labeling of the polymodal zones indicated that they receive parallel thalamocortical projections primarily from non-specific auditory and visual thalamic nuclei including the medial and dorsal divisions of the medial geniculate nucleus (MGm and MGd), the suprageniculate nucleus (SGN), and the lateral posterior nucleus (LP). The polymodal zone in visual cortex also receives specific projections from the dorsal division of the lateral geniculate nucleus (LGd). These data conform to a general model of thalamocortical organization in which specific thalamic nuclei with a high degree of modality specificity make restricted projections to primary sensory cortex and parts of secondary sensory cortex, and association thalamic nuclei with a high degree of sensory convergence make more divergent cortical projections. Primary and secondary sensory cortex, as well as distinct zones of polysensory cortex appear to be activated in tandem via parallel thalamocortical projections. Thus, the cerebral cortex must have simultaneous access to both unimodal and polymodal sensory information.

MEG and ECoG localization accuracy test.

We tested the localization accuracy of magnetoencephalography (MEG) and electrocorticography (ECoG) for a current dipole in a saline filled sphere at depths ranging from 1 to 6 cm at 1 cm intervals. We used standard neuromagnetometer placements and subdural electrode grids, previously employed for patient studies, with precise measurements of sensor and electrode locations with a 3-dimensional spatial digitizer. MEG and ECoG had comparable accuracy with mean errors of 1.5 and 1.8 mm, respectively. It appears that use of the spatial digitizer increases accuracy for both MEG and EGoG localizations. The larger errors in the ECoG with increasing depths could be attributed to under-sampling of the spatial pattern of the field which spreads out with deeper sources. It should be noted that in clinical applications a grid of the dimensions used here would most typically be used for superficial sources on the cortex with depth recordings being preferred for investigations of deep epileptogenic activity. Results are encouraging for continued development of non-invasive MEG methods for further definition of epileptogenic zones in the brain.

Comparisons of MEG, EEG, and ECoG source localization in neocortical partial epilepsy in humans.

In order to delineate the characteristics of epileptic spikes, 1946 different spikes were studied in 6 patients with complex partial epilepsy. Non-invasive MEG and EEG source analysis of interictal spikes were contrasted to ECoG localization, surgical outcome and presence of lesions on MRI. Results indicated that: (1) using the most frequent occurring spike topography patterns from a large sample of spikes improved goodness-of-fit values for both MEG and EEG localization, (2) when spike patterns could be appropriately matched on several successive MEG measurements to provide an adequate matrix (3 of 6 subjects), there was excellent agreement between MEG dipole sources and ECoG sources as well as surgical outcome and presence of MRI lesions, (3) EEG source analyses also gave good results but not as consistently as MEG.

The anatomic organization of evoked potentials in rat parietal cortex: electrically evoked commissural responses.

1. Two 8 x 8 channel microelectrode arrays were positioned over 3.5 x 3.5 mm2 areas in homologous regions of right and left parietal cortex of four rats. Potentials were evoked by delivering epicortical electrical stimulation to each electrode on one hemisphere while mapping the commissural response from the contralateral array. Spatial distributions of the electrically evoked potential (EECP) complex were compared directly with cytochrome oxidase-stained sections of the recorded region. 2. Electrode sites most capable of eliciting a commissural EECP were arranged along a diagonal band extending medially from the rostral to caudal region of each electrode array, approximating the pattern of dysgranular cortex separating primary auditory (Te1) from primary somatosensory (Par1) cortex. Electrode sites in the rostromedial and caudolateral region were ineffectual in eliciting an EECP in either hemisphere. Stimulation sites within secondary visual cortex (Oc2L) also produced strong responses. Only weak responses were elicited from stimulation of Te1 and no EECP could be evoked when stimulating within Par1. 3. When an EECP in the maximally sensitive diagonal region was elicited, its spatial distribution was typically asymmetrical throughout the recording array; the response was largest along a diagonal region also extending medially from the rostral to caudal area of each electrode array. Thus the pattern of EECP in each hemisphere closely matched the pattern of electrically excitable regions in the contralateral hemisphere. 4. The EECP was usually heterogeneous. EECP distributions within the strongly responding diagonal area often formed two regions of maximum amplitude separated by a less active zone. Although responses in Te1 were significantly weaker than those in the adjacent dysgranular cortex, they also revealed a heterogeneous spatial distribution with multiple closely spaced maxima. Only responses in Oc2L appeared consistently homogeneous, with a single maximum representing the EECP. 5. These results provide functional evidence supporting a model of parietal cortex in which there are two basic types of recipient regions, densely granular regions, which are the termination sites of specific thalamocortical fibers, and dysgranular or agranular regions, which receive both ipsilateral and contralateral projections. The functional parceling of rodent parietal cortex on the basis of the spatial and temporal distribution of the epicortical evoked potential complex may be superimposed onto the anatomic parceling into granular and dysgranular zones. Implications for stages of sensory information processing are discussed.

A horseradish peroxidase study of parallel thalamocortical projections responsible for the generation of mid-latency auditory-evoked potentials.

Mid-latency auditory-evoked potentials (MAEP) were recorded from the parietotemporal region of the rat using a high spatial resolution epicortical multielectrode array. Horseradish peroxidase was injected into regions of primary and secondary auditory cortex which generate spatially and temporally distinct components of the MAEP complex to retrogradely label their thalamocortical projections. These data provide anatomical evidence for three parallel thalamocortical projection systems, originating in the ventral, dorsal and medial subdivisions of the medial geniculate nucleus, which may be responsible for the asynchronous activation of three distinct subpopulations of cortical neurons giving rise to components of the MAEP complex. Specific and non-specific characteristics of the thalamocortical projections are discussed.

Polysensory evoked potentials in rat parietotemporal cortex: combined auditory and somatosensory responses.

A 64 channel microelectrode array was used to map auditory evoked potentials (AEP), somatosensory evoked potentials (SEP) as well as combined auditory and somatosensory evoked potentials (ASEP) from a 7 x 7 mm2 area in rat parietotemporal neocortex. Cytochrome oxidase (CO) stained sections of layer IV were obtained in the same animals to provide anatomical information underlying epicortical field potentials. Epicortical responses evoked by click or vibrissa stimuli replicated earlier findings from our laboratory, and appeared as a family of waveforms centered on primary auditory (AI) or somatosensory (SI) cortical areas as determined from CO histology. Selective microinjections of HRP to AI and SI further confirmed their specific sensory relay nuclei in the thalamus. A small polysensory area between AI and SI, responded uniquely with an enhanced negative sharp wave to combined auditory and somatosensory stimuli. HRP retrograde labeling revealed that the thalamocortical projections to this area were from the posterior nuclear group (Po) and medial division of the medial geniculate (MGm). These data establish close relationships between epicortical AEP, SEP, and especially ASEP and corresponding cortical structures and thalamocortical projections. The neurogenesis of unimodal and polysensory evoked potentials is discussed in terms of specific and non-specific systems.