Experience-dependent changes in function and anatomy of adult barrel cortex

Manipulations of sensory input to vibrissal mechanoreceptors can modify columnar functioning of the barrel cortex in adult animals. In mice, partial vibrissectomy sparing one row of vibrissae in young adults results 7 days later in an increase in the functional cortical column activated by the spared whiskers and visualized with 2-deoxyglucose autoradiography. The increase in the extent of the labelled area is visible in all cortical layers, but particularly in layer V, where the metabolic labelling is more intense in the representation of the spared vibrissae. Two months after vibrissectomy the enlargement of the labelled area is accentuated. Deprivation of a row of vibrissae results in a decrease in the areal extent of its cortical representation. Investigations of cortico-cortical connections carried out in living slices of the barrel cortex of mice 2 months after vibrissectomy sparing one row of whiskers, revealed elongation and increased branching of axons originating in the spared cortical column. The dendritic spine density was increased on the basal dendrites of layer V pyramidal neurons of the spared column and decreased on layer III apical dendrites of the deprived column. Thus, prolonged changes in functional activation of adult barrel cortex are accompanied by rearrangement of cortico-cortical circuitry.     

Neonatal serotonin depletion modifies development but not plasticity in rat barrel cortex

Effects of serotonin depletion (induced by neonatal injection of 5,7-dihydroxytryptamine) upon dimensions of cortical barrels and their metabolic activation, and upon effects of neonatal vibrissectomy sparing row C, were examined in 1-month-old rats. Dimensions of row C barrels, and of [14C]2-deoxyglucose (2-DG) labelling in the cortex obtained after stimulation of the row C vibrissae, were measured. Serotonin depletion did not change dimensions of barrels, but reduced the extent of 2-DG labelling of cortical representation of the row C whiskers by 30%. Vibrissectomy sparing this row resulted in an expansion of the row C barrels and of 2-DG labelling in the barrel cortex that were similar in both control and serotonin-depleted rats.     

Ministrokes in rat barrel cortex

BACKGROUND AND PURPOSE: Many stroke models in rats are based on occlusion of the middle cerebral artery, which supplies a significant portion of multifunctional cortical and deep structures in the cerebral hemisphere. The purpose of this study was to develop a model for direct observation in real time of blood flow in and around focal ischemic regions of the cortex of known function. METHODS: Cranial windows were placed over the parietal cortex of adult Wistar and Sprague-Dawley rats anesthetized with ketamine and xylazine. Whisker barrel cortex responding to stimulation of the contralateral whiskers was identified by an intrinsic optical signal. Transits of vital dyes were recorded by videomicroscopy before and after ligation of three to six branches and major collaterals of the middle cerebral artery through the dura. Infarcts were demonstrated with triphenyl-tetrazolium chloride staining; their relation to barrel cortex was determined by Nissl and cytochrome oxidase histology. RESULTS: Reduced blood flow in small ischemic regions was outlined by patient blue violet in the surrounding nonischemic area; arteriovenous latencies increased more than four times in ischemic cortex. Infarcts,typically 3 mm or less, were seen at 24 hours in 8 of 16 Wistar and 9 of 9 Sprague-Dawley rats. The ministrokes were confirmed by histology to be in the somatosensory cortex. CONCLUSIONS: This model of local ischemia, produced deliberately in the functionally defined barrel cortex in rats, leads to ministrokes. Changes can be followed by videomicroscopy as they develop, and processes of recovery can potentially be monitored. Infarcts are confirmed by histology for their location and extent in the somatic representation.     

Long-term potentiation in vivo in layers II/III of rat barrel cortex

Long-term potentiation was studied in vivo in the rat barrel cortex. It was found that LTP lasting several hours could be induced in layer II/III by tetanic stimuli applied in layer IV. The probability of inducing LTP at a given site was high (86%) provided that the electrodes were not displaced too far horizontally. LTP was not observed if the stimulating electrode was located on the far side of the neighbouring barrel-column from the recording electrode. The strongest LTP was induced by stimulating layer IV septal locations or the edge of the barrel and recording in the near half of the neighbouring barrel. However, examples were found of LTP from layer IV to II/III within the same barrel, within the same septum and from barrel to adjacent septum. The probability of inducing LTP on a particular occasion was greatly increased by iontophoresis of bicuculline at the recording site during the tetanus (from 20 to 55% judged by a change in peak amplitude). The average increase in the peak amplitude was 29 +/- 3.2% for protocol 1 (urethane anesthesia, monopolar stimulation) and 23 +/- 7% for protocol 2 (barbiturate anesthesia, bipolar stimulation). The probability of inducing LTP was greater if the first tetanus was accompanied by BMI application (67%) than for any subsequent attempts (39%). These results suggest it should be possible to study the effect of LTP on sensory processing in defined positions within the barrel field.     

Intrinsic inhibitory pathways in mouse barrel cortex

The organization of intrinsic connections in the mouse somatosensory cortex was studied by combining tract-tracing and immunocytochemical techniques. Injections of HRP or fluorescent beads were made into the supragranular or infragranular layers of the posteriomedial barrel subfield. Numerous cells were retrogradely labeled within a vertical column centered on each injection site. Retrogradely labeled cells were also found > 3 mm horizontal to the injection. Dual-label immunocytochemistry identified the population of inhibitory, GABAergic cells forming intrinsic horizontal connections. Double-labeled cells were found predominantly within a 200 microns radius horizontal to an injection site. These findings indicate that intrinsic inhibitory pathways in the barrel cortex do not provide a substrate for direct GABAergic interactions among barrel columns, and that inter-columnar interactions are primarily excitatory.     

Innervation of VIP-immunoreactive neurons by the ventroposteromedial thalamic nucleus in the barrel cortex of the rat

We investigated the synaptic terminals of fibers originating in the ventroposteromedial thalamic nucleus (VPM) and projecting to the main input layers (IV/III) of the rat posteromedial barrel subfield. It was our aim to determine whether or not the subpopulation of vasoactive intestinal polypeptide (VIP)-immunoreactive neurons in these layers are directly innervated by the sensory thalamus. Anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and immunohistochemistry for VIP were combined for correlated light and electron microscopic examination. Columns of cortical tissue were well defined by barrel-like patches of PHA-L-labeled fibers and boutons in layers IV and III. Within these columns VIP-immunoreactive perikarya were located mainly in supragranular layers. Marked perikarya were also seen in infragranular layers, but their immunoreactivity was often weaker. Granular layer IV, which is the main terminal field for thalamic fibers, contained fewer VIP neurons than supragranular layers. In the light microscope, however, PHA-L-labeled fibers appeared to contact the somata or proximal dendrites of 60-86% of the layer IV VIP neurons . By contrast, only 18-35% of the VIP neurons in the supragranular layers, which receive a moderately dense projection from the VPM, appeared to be contacted. PHA-L-labeled boutons were seen close to 13-25% of infragranular VIP-positive cells. Electron microscopy showed that thalamic fibers formed at most four asymmetric synapses on a single layer IV, VIP-positive neuron. Although the proportion of VIP-positive neurons with labeled synapses was lower in supragranular layers, most of them shared multiple asymmetric synapses with labeled thalamic fibers. Up to six labeled synapses were seen on individual VIP neurons in layer III. We conclude that subpopulations of VIP-immunoreactive neurons, located in layers IV, III, and II are directly innervated by the VPM. These neurons may be involved in the initial stages of cortical processing of sensory information from the large, mystacial vibrissae. Since VIP is known to be colocalized with the inhibitory transmitter GABA, it is likely that VIP neurons participate in the shaping of the receptive fields in the barrel cortex.     

Experience-dependent cell survival in the maternal rat brain.

Postpartum maternal experience produces long-lasting changes in maternal behavior in the mother rat, which can be altered by early-life isolation. Postpartum experience also affects the regulation of adult neurogenesis in the neural circuit underlying maternal behavior, in a region-specific manner. Female rats were reared either with their mothers (MR) or in isolation in an artificial rearing (AR) paradigm. In adulthood, rats were mated and separated from their pups at birth. The following day, dams were injected with a mitotic marker and either allowed to interact with pups (maternal experience) or left alone. Results show that MR rats that acquire a later maternal experience show increases in cell survival in parts of the excitatory limb of the maternal neural network (bed nucleus of the stria terminalis and nucleus accumbens), but no changes in the inhibitory limb (amygdala). In comparison to AR inexperienced rats, AR maternally experienced rats show no increases in cell survival in the excitatory limb, but a striking reduction in cell survival in the inhibitory limb. The results suggest that early preweaning maternal isolation alters the structural plasticity that occurs following a postpartum maternal experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning-induced physiological memory in adult primary auditory cortex: receptive fields plasticity, model, and mechanisms

It is well established that the functional organization of adult sensory cortices, including the auditory cortex, can be modified by deafferentation, sensory deprivation, or selective sensory stimulation. This paper reviews evidence establishing that the adult primary auditory cortex develops physiological plasticity during learning. Determination of frequency receptive fields before and at various times following aversive classical conditioning and instrumental avoidance learning in the guinea pig reveals increased neuronal responses to the pure tone frequency used as a conditioned stimulus (CS). In contrast, responses to the pretraining best frequency and other non-CS frequencies are decreased. These opposite changes are often sufficient to shift cellular tuning toward or even to the frequency of the CS. Learning-induced receptive field (RF) plasticity (i) is associative (requires pairing tone and shock), (ii) highly specific to the CS frequency (e.g., limited to this frequency +/- a small fraction of an octave), (iii) discriminative (specific increased response to a reinforced CS+ frequency but decreased response to a nonreinforced CS- frequency), (iv) develops extremely rapidly (within 5 trials, the fewest trials tested), and (v) is retained indefinitely (tested to 8 weeks). Moreover, RF plasticity is robust and not due to arousal, but can be expressed in the deeply anesthetized subject. Because learning- induced RF plasticity has the major characteristics of associative memory, it is therefore referred to as "physiological memory". We developed a model of RF plasticity based on convergence in the auditory cortex of nucleus basalis cholinergic effects acting at muscarinic receptors, with lemniscal and nonlemniscal frequency information from the ventral and magnocellular divisions of the medial geniculate nucleus, respectively. In the model, the specificity of RF plasticity is dependent on Hebbian rules of covariance. This aspect was confirmed in vivo using microstimulation techniques. Further, the model predicts that pairing a tone with activation of the nucleus basalis is sufficient to induce RF plasticity similar to that obtained in behavioral learning. This prediction has been confirmed. Additional tests of the model are described. RF plasticity is thought to translate the acquired significance of sound into an increased frequency representation of behaviorally important stimuli.     

Phospholipase C-beta1 expression correlates with neuronal differentiation and synaptic plasticity in rat somatosensory cortex

Receptor-mediated signal transduction is thought to play an important role in neuronal differentiation and the modification of synaptic connections during brain development. The intracellular signalling molecule phospholipase C-beta1 (PLC-beta1), which is activated via specific neurotransmitter receptors, has recently been implicated in activity-dependent plasticity in the cat visual cortex. PLC-beta1 has been shown to be concentrated in an intermediate compartment-like organelle, the botrysome, which is present in 5-week-old, but not adult, cat cortical neurons. We have characterized the spatial and temporal regulation of PLC-beta1 expression in the developing rat cerebral cortex. PLC-beta1-positive botrysome-like organelles are observed during early postnatal cortical development, but not at postnatal day 14 or later stages. In the postnatal somatosensory cortex, there is also striking spatial variation in diffuse neuropilar immunoreactivity of layer IV and above, in a pattern corresponding to the thalamocortical recipient zones known as barrels. This expression pattern is specific to the developing barrel field and is most distinct at postnatal days 4-7, when cellular components of barrels are capable of activity-dependent modification. During later stages of cortical maturation, stained botrysomes disappear, expression of PLC-beta1 is down-regulated and only diffuse immunoreactivity remains in dendritic processes. Our results are consistent with a role for PLC-beta1 in activity-dependent, receptor-mediated neuronal plasticity during development of the somatosensory cortex.     

Modular distribution of vasoactive intestinal polypeptide in the rat barrel cortex: changes induced by neonatal removal of vibrissae

The Nef gene of the human and simian immunodeficiency viruses HIV and SIV has been implicated in pathogenicity; however, the mechanism by which Nef induces disease is still unknown. An impact on signal transduction in cells has been suggested by the interaction of Nef from an HIV-1 strain and tyrosine kinases like HCK and LCK as well as serine/threonine kinases. We have confirmed the binding of HCK to HIV-1 subtype B Nef and demonstrated an equally strong interaction with a subtype E Nef protein but weaker binding to Nef of HIV-2 subtype A (HIV-2D194). No binding, however, was observed to HIV-2 subtype B Nef (HIV-2D205). Instead, this protein bound to a novel cellular protein, Nefin 1, with characteristics of an adaptor protein and strong expression in all human hematopoietic tissues. Nefin 1 binds through an amino-terminal domain, which is related to SH3 domains. For interaction of Nef with Nefin 1, the PxxP motif and the three-dimensional conformation of the molecule appear necessary. In conclusion, this study demonstrates that Nef proteins of divergent strains of HIV-1 and HIV-2 may use different elements of signal transduction pathways for the induction of pathogenicity in vivo.     

Silent synapses in the developing rat visual cortex: evidence for postsynaptic expression of synaptic plasticity

In the developing visual cortex activity-dependent refinement of synaptic connectivity is thought to involve synaptic plasticity processes analogous to long-term potentiation (LTP). The recently described conversion of so-called silent synapses to functional ones might underlie some forms of LTP. Using whole-cell recording and minimal stimulation procedures in immature pyramidal neurons, we demonstrate here the existence of functionally silent synapses, i.e., glutamatergic synapses that show only NMDA receptor-mediated transmission, in the neonatal rat visual cortex. The incidence of silent synapses strongly decreased during early postnatal development. After pairing presynaptic stimulation with postsynaptic depolarization, silent synapses were converted to functional ones in an LTP-like manner, as indicated by the long-lasting induction of AMPA receptor-mediated synaptic transmission. This conversion was dependent on the activation of NMDA receptors during the pairing protocol. The selective activation of NMDA receptors at silent synapses could be explained presynaptically by assuming a lower glutamate concentration compared with functional ones. However, we found no differences in glutamate concentration-dependent properties of NMDA receptor-mediated PSCs, suggesting that synaptic glutamate concentration is similar in silent and functional synapses. Our results thus support a postsynaptic mechanism underlying silent synapses, i.e., that they do not contain functional AMPA receptors. Synaptic plasticity at silent synapses might be expressed postsynaptically by modification of nonfunctional AMPA receptors or rapid membrane insertion of AMPA receptors. This conversion of silent synapses to functional ones might play a major role in activity-dependent synaptic refinement during development of the visual cortex.     

Experience-dependent changes in exploratory behavior in the adult rat (Rattus norvegicus): Overall activity level and interactions with objects.

In a previous investigation, Renner and Rosenzweig reported that in juvenile rats some aspects of interaction with objects are affected by experience history, but that experience does not affect overall amount of exploratory behavior. In order to examine the plasticity of this behavioral system in adult rats, 20 male rats of the Berkeley S? strain were placed at 90 days of age into enriched (EC) and impoverished (IC) conditions. After 30 days, each was placed individually into a dimly illuminated arena with several objects for 10-min periods on two successive days. EC subjects reared significantly more and showed significantly longer and more complex bouts of interaction with objects than did IC subjects, including both manipulable (M) and nonmanipulable (N) objects. EC subjects were also more likely to interact with objects. All subjects interacted more with N than M objects, but EC subjects were more likely than IC subjects to climb upon the N objects. These relatively specific behavioral alterations suggest differences in the information that these animals could gather during exploration. These results, when considered in conjunction with those of the previous study, show that the qualitative aspects of exploratory behavior are dissociable from the quantity of exploration exhibited. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute plasticity in the human somatosensory cortex following amputation

We studied a patient after amputation of an arm and found that in less than 24 h stimuli applied on the ipsilateral face were referred in a precise, topographically organized, modality-specific manner to distinct points on the phantom. Functional magnetic resonance imaging (fMRI) performed one month later showed that brush-evoked activity in the brain demonstrates objective signal changes which correlate with perceptual changes in the phantom hand. This finding in humans corresponds to the observations of immediate plasticity in cortical pathways described in animals, including primates. The results suggest that reorganization of sensory pathways occurs very soon after amputation in humans, potentially due to the unmasking of ordinarily silent inputs rather than sprouting of new axon terminals.     

Structure and plasticity of newly formed adult synapses: a morphometric study in the rat hippocampus

Increasing evidence suggests that synaptic structure represents a plastic feature of the neuron, although the plastic nature of newly formed and existing adult synapses has not yet been fully characterized. Following ipsilateral entorhinal cortical lesions, the rat dentate gyrus offers an excellent model for studying synaptogenesis and plasticity in the adult central nervous system. Unilateral entorhinal lesions were performed in young adult male rats. Synaptic counts and structural features were quantified at 3, 6, 10, 15, and 30 days post-lesion. The lesions resulted in an 88% synaptic loss in the denervated dentate middle molecular layer, which was followed by a period of rapid synaptogenesis. Synaptic element size decreased during the period of maximal synaptogenesis, which was associated with a peak in the presence of non-vesicular and perforated synapses. Following this period, synapses showed a gradual increase in the size of their pre- and postsynaptic elements. These data support the suggestion that newly formed adult synapses have smaller synaptic components than existing adult synapses (resembling synapses seen during development), and increase in size over time with usage. The results are discussed in terms of synaptic structural development and plasticity in the adult central nervous system.     

Tetraethylammonium-induced synaptic plasticity in rat neocortex

Recordings were obtained from neurons in layer II/III of slices of rat frontal cortex maintained in vitro. We investigated whether brief application of the potassium channel blocker tetraethylammonium (TEA), which induces a novel form of synaptic plasticity in the CA1 region of the hippocampus referred to as LTPK, evokes similar responses in neocortex. Consistent with previous findings, TEA produced a persistent enhancement of excitatory transmission, which was independent of NMDA receptor activation but required the activation of nifedipine-sensitive voltage-dependent Ca2+ channels (VDCC), presumably the L-type. We also observed a persistent enhancement of presumptive CI(-)-dependent GABAA receptor-mediated transmission. Enhancement of excitatory and inhibitory synaptic transmission did not require activation of synapses with electrical stimulation during TEA application. The enhancement of excitatory, but not inhibitory synaptic transmission, was blocked when the Ca2+ chelator 1,2-bis(2-aminophenoxy)-ethane N,N,N',N'-tetraacetic acid (BAPTA) was included in the recording electrode. Under voltage clamp conditions that minimized the activation of L-type channels robust enhancement of both excitatory and inhibitory transmission was still observed. No enhancement of excitatory synaptic transmission was observed in the presence of NiCl2, a putative T-type channel blocker. The possible involvement of kinase activation was studied by including the non-specific and competitive kinase inhibitor (+/-)-1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) in the patch pipette. H-7 retarded the time course and reduced the magnitude of the enhancement of excitatory transmission. These results suggest that TEA-induced enhancement of excitatory transmission in the neocortex requires entry of Ca2+ into the postsynaptic neuron via VDCCs and possibly the activation of a kinase.     

Widespread activation of barrel cortex by small numbers of neonatally spared whiskers

Activity-dependent plasticity in rodent whisker barrel cortex was examined by means of high-resolution 2-deoxyglucose (2-DG) with immunohistochemical double labeling. Hamsters with all but one, two, or four follicles ablated on postnatal day 7 received 2-DG injections as adults. Autoradiograms of follicle-ablated animals showed heavy activation of the entire barrel field during normal behavior, despite the missing whiskers. The intensity of 2-DG labeling was significantly reduced if the whiskers spared after follicle ablation were trimmed prior to the 2-DG injection, demonstrating that the widespread activation was driven by the spared whiskers. This widespread metabolic activation of the adult barrel field after neonatal follicle ablation was in sharp contrast to the somatotopically appropriate 2-DG labeling in barrel fields of normal adults subject to acute trimming of most whiskers, but was similar to that seen in normal adult animals with all whiskers intact. The results demonstrate large-scale plasticity of barrel circuitry following neonatal sensory deprivation, and provide a powerful functional anatomical setting to investigate underlying mechanisms.     

GABAergic neurons in barrel cortex show strong, whisker-dependent metabolic activation during normal behavior

Electrophysiological data from the rodent whisker/barrel cortex indicate that GABAergic, presumed inhibitory, neurons respond more vigorously to stimulation than glutamatergic, presumed excitatory, cells. However, these data represent very small neuronal samples in restrained, anesthetized, or narcotized animals or in cortical slices. Histochemical data from primate visual cortex, stained for the mitochondrial enzyme cytochrome oxidase (CO) and for GABA, show that GABAergic neurons are more highly reactive for CO than glutamatergic cells, indicating that inhibitory neurons are chronically more active than excitatory neurons but leaving doubt about the short-term stimulus dependence of this activation. Taken together, these results suggest that highly active inhibitory neurons powerfully influence relatively inactive excitatory cells but do not demonstrate directly the relative activities of excitatory and inhibitory neurons in the cortex during normal behavior. We used a novel double-labeling technique to approach the issue of excitatory and inhibitory neuronal activation during behavior. Our technique combines high-resolution 2-deoxyglucose (2DG), immunohistochemical staining for neurotransmitter-specific antibodies, and automated image analysis to collect the data. We find that putative inhibitory neurons in barrel cortex of behaving animals are, on average, much more heavily 2DG-labeled than presumed excitatory cells, a pattern not seen in animals anesthetized at the time of 2DG injection. This metabolic activation is dependent specifically on sensory inputs from the whiskers, because acute trimming of most whiskers greatly reduces 2DG labeling in both cell classes in columns corresponding to trimmed whiskers. Our results provide confirmation of the active GABAergic cell hypothesis suggested by CO and single-unit data. We conclude that strong activation of inhibitory cortical neurons must confer selective advantages that compensate for its inherent energy inefficiency.     

Development of the barrels and barrel field in the somatosensory cortex of the mouse

Barrels of the PMBSF of the mouse somatosensory cortex become apparent in Nissl-stained tangential sections simultaneously, on the fourth postnatal day. At this time they are miniatures of those in the adult and are situated in the deepest sublamina of the trilaminar cortical plate. An early barrel appears as a patch of decreased cell density: the prospective hollow of the barrel. Septa become noticeable during the sixth postnatal day. From that period to adulthood, the relative contribution of the PMBSF to the total cortical surface area increases -- an increase that goes against one's expectation: the barrel related periphery matures very early and so does the central, lateral region of the cortex. Barrel growth parallel to the pial surface is greater along the major axes than along the minor axes. By using the barrels to identify prospective layer IV in immature cortex, we could determine that layers V and VI attain their adult height during the sixth postnatal day -- an age when prospective layers I-IV are only half their adult height. The onset of barrel formation coincides with the moment after which injury to the pertinent somatosensory periphery (the vibrissal papillae) no longer causes profound alterations in barrel morphology.     

Lesion-induced plasticity of central neurons: sprouting of single fibres in the rat hippocampus after unilateral entorhinal cortex lesion

In response to a central nervous system trauma surviving neurons reorganize their connections and form new synapses that replace those lost by the lesion. A well established in vivo system for the analysis of this lesion-induced plasticity is the reorganization of the fascia dentata following unilateral entorhinal cortex lesions in rats. After general considerations of neuronal reorganization following a central nervous system trauma, this review focuses on the sprouting of single fibres in the rat hippocampus after entorhinal lesion and the molecular factors which may regulate this process. First, the connectivity of the fascia dentata in control animals is reviewed and previously unknown commissural fibers to the outer molecular layer and entorhinal fibres to the inner molecular layer are characterized. Second, sprouting of commissural and crossed entorhinal fibres after entorhinal cortex lesion is described. Single fibres sprout by forming additional collaterals, axonal extensions, boutons, and tangle-like axon formations. It is pointed out that the sprouting after entorhinal lesion mainly involves unlesioned fibre systems terminating within the layer of fibre degeneration and is therefore layer-specific. Third, molecular changes associated with axonal growth and synapse formation are considered. In this context, the role of adhesion molecules, glial cells, and neurotrophic factors for the sprouting process are discussed. Finally, an involvement of sprouting processes in the formation of neuritic plaques in Alzheimer's disease is reviewed and discussed with regard to the axonal tangle-like formations observed after entorhinal cortex lesion.