Corticocortical associative neurons expressing latexin: specific cortical connectivity formed in vivo and in vitro.

Latexin, a carboxypeptidase A inhibitor, is expressed in a subset of neurons in the infragranular layers of the lateral cortex in the rat. We here show that latexin-expressing neurons exhibit ultrastructural features common to cortical pyramidal neurons. We show in combined retrograde tracing and immunofluorescent experiments that latexin-expressing neurons contribute to specific corticocortical pathways. Thus, injections of the retrograde tracer fluorogold into either the primary somatosensory (SI) or the primary motor (MI) cortical area labeled many latexin-expressing neurons in the infragranular layers of the secondary somatosensory (SII) and visceral sensory (Vi) areas. In contrast, tracer injections involving the thalamus, striatum, or contralateral SII and Vi exclusively labeled latexin-nonexpressing neurons in both the SII and Vi. Finally, we show that the correct corticocortical projections can be formed in organotypic slice cultures in vitro from latexin-expressing neurons: when slices of developing SII were cocultured with those from the SI and the thalamus, latexin-immunoreactive neurons in the SII projected preferentially to their normal SI target. The specific connectivity formed in vivo and in vitro by this molecularly distinct neuronal population reveals its characteristic manner of cortical organization and provides a unique model system to analyze mechanisms underlying the formation of precise corticocortical pathways.     

Localization of the glutamine transporter SNAT1 in rat cerebral cortex and neighboring structures, with a note on its localization in human cortex

SNAT1 mediates glutamine (Gln) influx into neurons and is believed to replenish the transmitters pools of glutamate (Glu) and gamma-aminobutyric acid (GABA). We investigated its distribution and cellular localization in the cerebral cortex and neighboring regions of rats and humans using light and electron microscopic immunocytochemical methods with specific antibodies. In the first somatic sensory cortex of rats and in areas 9, 10, 21 and 46 of the human cortex, numerous SNAT1-positive (+) cells were present in the cortical parenchyma and in the white matter; >95% of SNAT1+ cells were neurons, but some were astrocytes. Most SNAT1+ cells were pyramidal neurons, but numerous non-pyramidal neurons were also observed: SNAT1/GABA double-labeling studies showed that SNAT1 is expressed in all GABA+ neurons. SNAT1/synaptophysin studies showed that <0.1% of all synaptophysin+ puncta coexpressed SNAT1. SNAT1 immunoreactivity (ir) was also in leptomeninges, ependymal cells and choroid plexus. Electron microscopic studies showed that neuronal SNAT1 ir was almost exclusively observed in perikarya and dendritic profiles. SNAT1 ir was also in distal astrocytic processes, including end feet profiles, and in leptomeninges. These findings suggest that the major function of SNAT1 is not to replenish the transmitter pools of Glu and GABA.     

The effects of morphine self-administration on cortical pyramidal cell structure in addiction-prone lewis rats

The consumption of drugs of abuse provokes sensitization, the development of tolerance, dependency, and eventually addiction. It is thought that these events are partially a consequence of drug-induced alterations in the organization of neuronal circuits in specific areas of the brain. In the present study, we have used intracellular injections of lucifer yellow to examine the alterations that may occur in cortical pyramidal neurons of addiction-prone Lewis rats following 15 days of self-administration of morphine. Specifically, the effects of morphine on the structure, size and branching complexity of the basal dendrites, and spine density were determined in the basal dendritic arbors of layer III pyramidal neurons in both the prelimbic and motor cortex. We found that following morphine self-administration, there was a reduction in the size and branching complexity of the dendritic arbors of pyramidal cells in the motor cortex. In contrast, prelimbic pyramidal neurons from these morphine-treated animals had larger and longer basal dendritic arbors. Furthermore, the spine density on pyramidal neurons was higher in both cortical regions of morphine self-administered rats. These results suggest that at least part of the behavioral changes produced by repeated opiate administration may be attributed to alterations in pyramidal cell structure.     

Regional, laminar and cellular distribution of immunoreactivity for ERbeta in the cerebral cortex of hormonally intact, postnatally developing male and female rats

Estrogen influences cerebral cortical development. Among the receptors involved are classical (ERalpha) and beta (ERbeta) intracellular estrogen receptors. In the first 2 weeks of postnatal life, cortical ERalpha is transiently expressed at much higher levels than in adulthood. In this study, development of ERbeta was examined by mapping ERbeta immunoreactivity in relation to major cortical regions, layers and cell types in postnatal male and female rats that were 1-28 postnatal days (PND) old. These studies revealed that ERbeta-immunoreactive nuclei were present in the allocortices on PND 1 but were not detected in isocortex until PND 7. Allocortical labeling was also higher on PND 1 than at all later ages, while in isocortical areas low numbers of ERbeta nuclei were seen on PND 7 that rose to higher, near adult densities by PND 21. Finally, double labeling showed that ERalpha was expressed mainly in neurons immunopositive for calretinin, while ERbeta was localized predominantly in parvalbumin-immunoreactive cells. Thus, the postnatal cortical developments of ERbeta and ERalpha occur according to different timetables, different patterns and in association with different cortical cells. It thus seems it likely that the two also make distinct contributions to postnatal cortical development and/or sexual differentiation.     

Regional, laminar, and cellular distribution of immunoreactivity for ER alpha and ER beta in the cerebral cortex of hormonally intact, adult male and female rats.

Behavioral, biochemical and anatomical studies suggest that estrogen stimulates structure and/or function in the adult cerebral cortex. The studies presented here used immunocytochemistry to map the alpha and beta isoforms of intracellular estrogen receptors (ER alpha, ER beta) in major subdivisions of adult rat cortex to identify potential sites for relevant receptor-mediated hormone actions. These studies revealed that immunoreactivity for ER alpha (ER alpha-IR) and ER beta (ER beta-IR) was present in most cortical areas, was associated exclusively with neurons, and was similar in males and females. Each receptor isoform also had its own unique distribution with respect to cortical regions, layers, and cells. In sensorimotor areas, for example, ER beta-IR was more prominent than ER alpha-IR, and was concentrated in layer V neurons that were immunoreactive for parvalbumin. In contrast, ER alpha-IR was scattered among parvalbumin-immunonegative cells in layers II/III and V/VI. Likewise, in entorhinal cortex, ER beta-IR was present in calbindin-containing cells in layers III-VI, while ER alpha-IR was restricted to small numbers of calbindin-negative neurons in infragranular layers. In sum, ER beta-IR and ER alpha-IR were differentially distributed both with respect to cortical compartments and with respect to each other. Accordingly, estrogen activation at these two sites may be anticipated to impact disparate sets of cortical circuits, cells, and functions.     

Neuronal and glial localization of NR1 and NR2A/B subunits of the NMDA receptor in the human cerebral cortex

N-Methyl-D-aspartate (NMDA) receptors play a critical role in many cortical functions and are implicated in several neuropsychiatric diseases. In this study, the cellular expression of the NMDAR1 (NR1) and NMDAR2A and B (NR2A and B) subunits was investigated in the human cerebral cortex by immunocytochemistry with antibodies that recognize the NR1 or the NR2A and B subunits of the NMDA receptor. In frontal (areas 10 and 46) and temporal (area 21) association cortices and the cingulofrontal transition cortex (area 32), NR1 and NR2A/B immunoreactivity (ir) were similar and were localized to numerous neurons in all cortical layers. NR1- and NR2A/B-positive neurons were mostly pyramidal cells, but some nonpyramidal neurons were also labeled. Electron-microscopic observations showed that NR1 and NR2A/B ir were similar. In all cases, labeling of dendrites and dendritic spines was intense. In addition, both NR1 and NR2A/B were consistently found in the axoplasm of some axon terminals and in distal astrocytic processes. This investigation revealed that numerous NMDA receptors are localized to dendritic spines, and that they are also localized to axon terminals and astrocytic processes. These findings suggest that the effects of cortical NMDA activation in the human cortex do not depend exclusively on the opening of NMDA channels located at postsynaptic sites, and that the localization of NMDA receptors is similar in a variety of mammalian species.     

Regional dendritic and spine variation in human cerebral cortex: a quantitative golgi study

The present study explored differences in dendritic/spine extent across several human cortical regions. Specifically, the basilar dendrites/spines of supragranular pyramidal cells were examined in eight Brodmann's areas (BA) arranged according to Benson's (1993, Behav Neurol 6:75-81) functional hierarchy: primary cortex (somatosensory, BA3-1-2; motor, BA4), unimodal cortex (Wernicke's area, BA22; Broca's area, BA44), heteromodal cortex (supple- mentary motor area, BA6beta; angular gyrus, BA39) and supramodal cortex (superior frontopolar zone, BA10; inferior frontopolar zone, BA11). To capture more general aspects of regional variability, primary and unimodal areas were designated as low integrative regions; heteromodal and supramodal areas were designated as high integrative regions. Tissue was obtained from the left hemisphere of 10 neurologically normal individuals (M(age) = 30 +/- 17 years; five males, five females) and stained with a modified rapid Golgi technique. Ten neurons were sampled from each cortical region (n = 800) and evaluated according to total dendritic length, mean segment length, dendritic segment count, dendritic spine number and dendritic spine density. Despite considerable inter-individual variation, there were significant differences across the eight Brodmann's areas and between the high and low integrative regions for all dendritic and spine measures. Dendritic systems in primary and unimodal regions were consistently less complex than in heteromodal and supramodal areas. The range within these rankings was substantial, with total dendritic length in BA10 being 31% greater than that in BA3-1-2, and dendritic spine number being 69% greater. These findings demonstrate that cortical regions involved in the early stages of processing (e.g. primary sensory areas) generally exhibit less complex dendritic/spine systems than those regions involved in the later stages of information processing (e.g. prefrontal cortex). This dendritic progression appears to reflect significant differences in the nature of cortical processing, with spine-dense neurons at hierarchically higher association levels integrating a broader range of synaptic input than those at lower cortical levels.     

Concurrent tonotopic processing streams in auditory cortex

The basis for multiple representations of equivalent frequency ranges in auditory cortex was studied with physiological and anatomical methods. Our goal was to trace the convergence of thalamic, commissural, and corticocortical information upon two tonotopic fields in the cat, the primary auditory cortex (AI) and the anterior auditory field (AAF). Both fields are among the first cortical levels of processing. After neurophysiological mapping of characteristic frequency, we injected different retrograde tracers at separate, frequency-matched loci in AI and AAF. We found differences in their projections that support the notion of largely segregated parallel processing streams in the auditory thalamus and cerebral cortex. In each field, ipsilateral cortical input amounts to approximately 70% of the number of cells projecting to an isofrequency domain, while commissural and thalamic sources are each approximately 15%. Labeled thalamic and cortical neurons were concentrated in tonotopically predicted regions and in smaller loci far from their spectrally predicted positions. The few double-labeled thalamic neurons (<2%) are consistent with the hypothesis that information to AI and AAF travels along independent processing streams despite widespread regional overlap of thalamic input sources. Double labeling is also sparse in both the corticocortical and commissural systems ( approximately 1%), confirming their independence. The segregation of frequency-specific channels within thalamic and cortical systems is consistent with a model of parallel processing in auditory cortex. The global convergence of cells outside the targeted frequency domain in AI and AAF could contribute to context-dependent processing and to intracortical plasticity and reorganization.     

Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex

The prefrontal cortex plays a key role in the control of higher brain functions and is involved in the pathophysiology and treatment of schizophrenia. Here we report that approximately 60% of the neurons in rat and mouse prefrontal cortex express 5-HT(1A) and/or 5-HT2A receptor mRNAs, which are highly co-localized (approximately 80%). The electrical stimulation of the dorsal and median raphe nuclei elicited 5-HT1A-mediated inhibitions and 5-HT2A-mediated excitations in identified pyramidal neurons recorded extracellularly in rat medial prefrontal cortex (mPFC). Opposite responses in the same pyramidal neuron could be evoked by stimulating the raphe nuclei at different coordinates, suggesting a precise connectivity between 5-HT neuronal subgroups and 5-HT1A and 5-HT2A receptors in pyramidal neurons. Microdialysis experiments showed that the increase in local 5-HT release evoked by the activation of 5-HT2A receptors in mPFC by DOI (5-HT2A/2C receptor agonist) was reversed by co-perfusion of 5-HT1A agonists. This inhibitory effect was antagonized by WAY-100635 and the prior inactivation of 5-HT1A receptors in rats and was absent in mice lacking 5-HT1A receptors. These observations help to clarify the interactions between the mPFC and the raphe nuclei, two key areas in psychiatric illnesses and improve our understanding of the action of atypical antipsychotics, acting through these 5-HT receptors.     

The pyramidal cell of the sensorimotor cortex of the macaque monkey: phenotypic variation

Recent studies have revealed striking differences in pyramidal cell structure among cortical regions involved in the processing of different functional modalities. For example, cells involved in visual processing show systematic variation, increasing in morphological complexity with rostral progression from V1 through extrastriate areas. Differences have also been identified between pyramidal cells in somatosensory, motor and prefrontal cortex, but the extent to which the pyramidal cell phenotype may vary between these functionally related cortical regions remains unknown. In the present study we investigated the structure of layer III pyramidal cells in somatosensory and motor areas 3b, 4, 5, 6 and 7b of the macaque monkey. Cells were intracellularly injected in fixed, flat-mounted cortical slices and analysed for morphometric parameters. The size of the basal dendritic arbours, the number of their branches and their spine density were found to vary systematically between areas. Namely, we found a trend for increasing complexity in dendritic arbour structure through areas 3b, 5 and 7b. A similar trend occurred through areas 4 and 6. The differences in arbour structure may determine the number of inputs received by neurons and may thus be an important factor in determining function at the cellular and systems level.     

Neural responses during interception of real and apparent circularly moving stimuli in motor cortex and area 7a

We recorded the neuronal activity in the arm area of the motor cortex and parietal area 7a of two monkeys during interception of stimuli moving in real and apparent motion. The stimulus moved along a circular path with one of five speeds (180-540 degrees/s), and was intercepted at 6 o'clock by exerting a force pulse on a semi-isometric joystick which controlled a cursor on the screen. The real stimuli were shown in adjacent positions every 16 ms, whereas in the apparent motion situation five stimuli were flashed successively at the vertices of a regular pentagon. The results showed, first, that a group of neurons in both areas above responded not only during the interception but also during a NOGO task in which the same stimuli were presented in the absence of a motor response. This finding suggests these areas are involved in both the processing of the stimulus as well as in the preparation and production of the interception movement. In addition, a group of motor cortical cells responded during the interception task but not during a center --> out task, in which the monkeys produced similar force pulses towards eight stationary targets. This group of cells may be engaged in sensorimotor transformations more specific to the interception of real and apparent moving stimuli. Finally, a multiple regression analysis revealed that the time-varying neuronal activity in area 7a and motor cortex was related to various aspects of stimulus motion and hand force in both the real and apparent motion conditions, with stimulus-related activity prevailing in area 7a and hand-related activity prevailing in motor cortex. In addition, the neural activity was selectively associated with the stimulus angle during real motion, whereas it was tightly correlated to the time-to-contact in the apparent motion condition, particularly in the motor cortex. Overall, these observations indicate that neurons in motor cortex and area 7a are processing different parameters of the stimulus depending on the kind of stimulus motion, and that this information is used in a predictive fashion in motor cortex to trigger the interception movement.     

In vivo excitation of GABA interneurons in the medial prefrontal cortex through 5-HT3 receptors

Serotonin (5-hydroxytryptamine, 5-HT) controls pyramidal cell activity in prefrontal cortex (PFC) through various receptors, in particular, 5-HT1A and 5-HT2A receptors. Here we report that the physiological stimulation of the raphe nuclei excites local, putatively GABAergic neurons in the prelimbic and cingulate areas of the rat PFC in vivo. These excitations had a latency of 36 +/- 4 ms and a duration of 69 +/- 9 ms and were blocked by the i.v. administration of the 5-HT3 receptor antagonists ondansetron and tropisetron. The latency and duration were shorter than those elicited through 5-HT2A receptors in pyramidal neurons of the same areas. Double in situ hybridization histochemistry showed the presence of GABAergic neurons expressing 5-HT3 receptor mRNA in PFC. These cells were more abundant in the cingulate, prelimbic and infralimbic areas, particularly in superficial layers. The percentages of GAD mRNA-positive neurons expressing 5-HT3 receptor mRNA in prelimbic cortex were 40, 18, 6 and 8% in layers I, II-III, V and VI, respectively, a distribution complementary to that of cells expressing 5-HT2A receptors. Overall, these results support an important role of 5-HT in the control of the excitability of apical dendrites of pyramidal neurons in the medial PFC through the activation of 5-HT3 receptors in GABAergic interneurons.     

Scheduling of monoaminergic neurotransmitter receptor expression in the primate neocortex during postnatal development.

Quantitative in vitro autoradiography was used to study the postnatal development of monoaminergic receptors (D1 and D2 dopaminergic, 5-HT1 and 5-HT2 serotonergic, and alpha 1, alpha 2, and beta noradrenergic sites) in the prefrontal, primary motor, somatosensory, and visual cortex of rhesus monkeys at birth and 1, 2, 4, 8, 12, 36, and 60 months of age. The density of all receptors studied increased rapidly within the first 2 postnatal months to levels as high as two times that recorded in the adults. After the fourth month, receptor density began a decline that subsided around the time of puberty. This course of developmental change was similar in all cortical layers and in all regions examined. However, the magnitude of the transient overproduction and eventual reduction in receptor density varied across the cortical layers and cytoarchitectonic areas in a manner specific to the individual receptor sites. Overall, cortical maturation was associated with the increased tendency of monoaminergic receptors to concentrate preferentially in the superficial cortical layers. The common developmental course of monoaminergic receptors in diverse cytoarchitectonic areas reveals an impressive coordination in the expression and regulation of these functionally relevant proteins in the cerebral cortex during infancy and adolescence.     

Comparison of Intrinsic Connectivity in Different Areas of Macaque Monkey Cerebral Cortex

We have used small injections of biocytin to label and comparepatterns of intreareal, laterally spreading projections of pyramidalneurons in a number of areas of macaque monkey cerebral cortex.In visual areas (V1, V2, and V4), somatosensory areas (3b, 1,and 2), and motor area 4, a punctate discontinuous pattern ofconnections is made from 200-µm-diameter biocytin injectionsin the superficial layers. In prefrontal cortex (areas 9 and46), stripe-like connectivity patterns are observed. In allareas of cortex examined, the width of the terminal-free gapsis closely scaled to the average diameter of terminal patches,or width of terminal stripes. In addition, both patch and gapdimensions match the average lateral spread of the dendriticfield of single pyramidal neurons in the superficial layersof the same cortical region. These architectural features ofthe connectional mosaics are constant despite a twofold differencein scale across cortical areas and different species. They thereforeappear to be fundamental features of cortical organization.A model is offered in which local circuit inhibitory "basket"interneurons, activated at the same time as excitatory pyramidalneurons, could veto pyramidal neuron connections within eithercircular or stripe-like domains; this could lead to the formationof the pattern of lateral connections observed in this study,and provides a framework for further theoretical studies ofcerebral cortex function.     

Search for color 'center(s)' in macaque visual cortex

It is often stated that color is selectively processed in cortical area V4, in both macaques and humans. However most recent data suggests that color is instead processed in region(s) antero-ventral to V4. Here we tested these two hypotheses in macaque visual cortex, where 'V4' was originally defined, and first described as color selective. Activity produced by equiluminant color-varying (versus luminance-varying) gratings was measured using double-label deoxyglucose in awake fixating macaques, in multiple areas of flattened visual cortex. Much of cortex was activated near-equally by both color- and luminance-varying stimuli. In remaining cortical regions, discrete color-biased columns were found in many cortical visual areas, whereas luminance-biased activity was found in only a few specific regions (V1 layer 4B and area MT). Consistent with a recent hypothesis, V4 was not uniquely specialized for color processing, but areas located antero-ventral to V4 (in/near TEO and anterior TE) showed more color-biased activity.     

Dendritic size of pyramidal neurons differs among mouse cortical regions

Neocortical circuits share anatomical and physiological similarities among different species and cortical areas. Because of this, a 'canonical' cortical microcircuit could form the functional unit of the neocortex and perform the same basic computation on different types of inputs. However, variations in pyramidal cell structure between different primate cortical areas exist, indicating that different cortical areas could be built out of different neuronal cell types. In the present study, we have investigated the dendritic architecture of 90 layer II/III pyramidal neurons located in different cortical regions along a rostrocaudal axis in the mouse neocortex, using, for the first time, a blind multidimensional analysis of over 150 morphological variables, rather than evaluating along single morphological parameters. These cortical regions included the secondary motor cortex (M2), the secondary somatosensory cortex (S2), and the lateral secondary visual cortex and association temporal cortex (V2L/TeA). Confirming earlier primate studies, we find that basal dendritic morphologies are characteristically different between different cortical regions. In addition, we demonstrate that these differences are not related to the physical location of the neuron and cannot be easily explained assuming rostrocaudal gradients within the cortex. Our data suggest that each cortical region is built with specific neuronal components.     

Organization of Rodent Auditory Cortex: Anterograde Transport of PHA-L from MGv to Temporal Neocortex

In the present study we analyzed the organization of the thalamocorticalprojections of the specific auditory relay nucleus of the thalamus,the ventral division of the medial geniculate body (MGv), usingthe anterograde axonal tracer Phaseolus vulgaris leucoagglutinin.All injections of MGv produced dense labeling of axonal fibersin temporal cortex. In all cases, labeled axons were predominantlyconcentrated in cortical layers III and IV and, to a lesserextent, at the junction of layers V and VI. Injections confinedto the medical regions of MGv, and specifically to the avoidnucleus of MGv (OV, parsovoidea), resulted in anterograde labelingof TE1, with minor labeling of the ventral quarter of TE1, designatedsubarea TE1v. Injections placed in lateral regions of MGv andoccupying the lateral ventral subnucleus (LV), or injectionsin the mediolateral center of MGv and occupying parts of LVand OV, also resulted in labeling of area TE1 and minor labelingof TE1v. However, these injections also produced labeling inareas TE2 and TE3. Thus, area TE1 (excluding subarea TE1v) receivesheavy projections from all aspects of MGv and appears to bethe core target of MGv. While regions of MGv also project tosurrounding cortical belt areas, these projections tend to belighter and to vary depending on the region of MGv examined.These results, together with other connectional findings, andcytoarchitectonic and physiological studies, suggest that TE1(possibly excluding subarea TE1v) is the primary auditory cortexin the rat.     

Interlaminar differences of intrinsic properties of pyramidal neurons in the auditory cortex of mice

Cortical information processing depends crucially upon intrinsic neuronal properties modulating a given synaptic input, in addition to integration of excitatory and inhibitory inputs. These intrinsic mechanisms are poorly understood in sensory cortex areas. We therefore investigated neuronal properties in slices of the auditory cortex (AC) of normal hearing mice using whole-cell patch-clamp recordings of pyramidal neurons in layers II/III, IV, V, and VI in the current- and voltage clamp mode. A total of 234 pyramidal neurons were included in the analysis revealing distinct laminar differences. Regular spiking (RS) neurons in layer II/III have significantly lower resting membrane potential, higher threshold for action potential generation, and larger K(ir) and Ih amplitudes compared with layer V and VI RS neurons. These currents could improve temporal resolution in the upper layers of the AC. Additionally, the presence of a T-type Ca2+ current could be an important factor of RS neurons in these upper layers to amplify temporally closely correlated inputs. Compared with upper layers, lower layers (V and VI) exhibit a higher relative abundance of intrinsic bursting neurons. These neurons may provide layer-specific transfer functions for interlaminar, intercortical, and corticofugal information processing.     

Morphological alteration and reduction of MAP2-immunoreactivity in pyramidal neurons of cerebral cortex in a rat model of focal cortical compression

Subdural hematoma causes cortical damage including brain tissue disruption, often resulting in neuronal dysfunction and neurological impairment. The aim of the present study was to identify the relationship between cerebral compression and neuronal injury. In this report, we investigated time-dependent morphological alterations within layers II, III, and V pyramidal neurons in the cerebral cortex, using Golgi-Cox staining and immunohistochemistry for microtubule-associated protein 2 (MAP2) in a rat model of focal cortical compression. An acryl pole was used to experimentally induce chronic cerebral compression by continuous pressure on the cortical surface. Changes in cellular morphology were examined at five survival time periods: 12?h and 1, 2, 3, and 4 weeks. The Golgi-Cox method revealed time-dependent alterations in dendritic length of apical and basilar dendrites of pyramidal neurons. The number of dendritic branch segments and spines of basilar dendrites were decreased in cells in layers II, III, and V. Immunohistochemical staining for MAP2 revealed changes in the intracellular distribution of immunoreactive materials. A significant reduction in MAP2 immunostaining was found in nerve cell bodies and apical dendrites of ipsilateral cortical neurons. The number of MAP2-immunoreactive neurons was significantly decreased at 12?h compared with the contralateral cerebral cortex in the same animal. Dendritic changes in layers II, III, and V pyramidal neurons were accompanied by reductions in intracellular MAP2-immunoreactive materials. The present results suggest that cortical compression causes alteration of cellular morphology as a consequence of injury, and that these morphological changes may be related to reductions in MAP2-immunoreactive materials.     

Cortical efferent control of subcortical sensory neurons by synaptic disinhibition

A long-standing hypothesis predicts that pyramidal neurons of the cerebral cortex control the influx of sensory information at the level of primary sensory representations areas. Yet little is known about the cellular mechanisms governing selective attention to behaviorally relevant objects in space. Neurons in the superficial layers of the superior colliculus are notably involved in this process, and they are directly targeted by retinal and cortical afferents. To study long-term and short-term effects of the visual cortex (VC) on subcortical visual neurons we established an in vitro model of the developing cortico-tectal projection. To this end, cortical explants expressing Green Fluorescent Protein were allowed to form connections with non-labeled dissociated tectal neurons. The presence of VC explants led to an enhancement of tectal activity by 2 mechanisms. First, glutamatergic input was increased. Second, intrinsic GABAergic inhibition was suppressed. The latter effect was shown to be acute and mediated through postsynaptic metabotropic glutamate receptor activation, G-protein acitivity, and endocannabinoid receptor activation. The VC-induced disinhibition was readily reversed by application of an mGluR antagonist. However, high-frequency activation of the glutamatergic cortico-tectal input turned the labile disinhibition into a persistent suppression of inhibition.