Whisker-related circuitry in the trigeminal nucleus principalis: Topographic precision

Abstract

Single whiskers are topographically represented in the trigeminal (V) nucleus principalis (PrV) by a set of cylindrical aggregates of primary afferent terminals and somata (barrelettes). This isomorphic pattern is transmitted to the thalamus and barrel cortex. However, it is not known if terminals in PrV from neighboring whiskers interdigitate so as to violate rules of spatial parcellation predicted by barrelette borders; nor is it known the extent to which higher order inputs are topographic. The existence of inter-whisker arbor overlap or diffuse higher order inputs would demand additional theoretical principles to account for single whisker dominance in PrV cell responses. In adult rats, first, primary afferent pairs responding to the same or neighboring whiskers and injected with Neurobiotin or horseradish peroxidase were rendered brown or black to color-code their terminal boutons. When collaterals from both fibers appeared in the same topographic plane through PrV, the percentage of the summed area of the two arbor envelopes that overlapped was computed. For same-whisker pairs, overlap was 5?±?6% (mean?±?SD). For within-row neighbors, overlap was 2?±?5%. For between-row neighbors, overlap was 1?±?4%. Second, the areas of whisker primary afferent arbors and their corresponding barrelettes in the PrV were compared. In the transverse plane, arbor envelopes significantly exceeded the areas of cytochrome oxidase-stained barrelettes; arbors often extended into neighboring barrelettes. Third, bulk tracing of the projections from the spinal V subnucleus interpolaris (SpVi) to the PrV revealed strict topography such that they connect same-whisker barrelettes in the SpVi and PrV. Thus, whisker primary afferents do not exclusively project to their corresponding PrV barrelette, whereas higher order SpVi inputs to the PrV are precisely topographic.     

The contribution of the principal and spinal trigeminal nuclei to the receptive field properties of thalamic VPM neurons in the rat

Primary sensory information from neurons innervating whisker follicles on one side of a rat's face is relayed primarily through two subnuclei of the brainstem trigeminal complex to the contralateral thalamus. The present experiments were undertaken to separate the contribution of the principal trigeminal nucleus (PrV) from that of the spinal trigeminal nucleus (SpV) to whisker evoked responses in the ventral posterior medial (VPM) nucleus in the adult rat thalamus. Extracellular single-unit responses of VPM neurons to controlled stimulation of the contralateral whiskers under urethane anesthesia were quantified in terms of receptive field size, modal latency, response probability and response magnitude. The SpV contribution to VPM cell responses was isolated by making kainic acid lesions of the PrV. The PrV contribution was ascertained by cutting the trigeminothalamic axons arising from SpV just before they cross the midline. After destruction of the PrV, the SpV pathway alone produced large receptive fields (mean: 9.04 whiskers) and long latency (mean: 11.07 ms) responses from VPM neurons. In contrast, PrV input alone (SpV disconnected) generated small receptive fields (mean: 1.06 whiskers) and shorter latency (mean: 6.74 ms) responses. With both pathways intact the average receptive field size was 2.4 whiskers and peak (modal) response latency was 7.33 ms. The responses with both pathways intact were significantly different from either pathway operating in isolation. Response probability and magnitude followed the same trend. We conclude that normal responses of individual VPM neurons represent the integration of input activity transmitted through both PrV and SpV pathways.     

Neuropathology in sensory,but not motor,brainstem nuclei of the rat whisker circuit after diffuse brain injury

Neurological dysfunction after traumatic brain injury (TBI) is associated with pathology in cortical, subcortical, and brainstem nuclei. Our laboratory has reported neuropathology and microglial activation in the somatosensory barrel cortex (S1BF) and ventral posterior medial thalamus (VPM) after diffuse TBI in the rat, which correlated with post-injury whisker sensory sensitivity. The present study extends our previous work by evaluating pathology in whisking-associated sensory and motor brainstem nuclei. Brains from adult, male rats were recovered over 1 month after midline fluid percussion or sham injury. The principal trigeminal nucleus (PrV, sensory nucleus) and facial nucleus (VIIN, motor nucleus) were examined for neuropathology (silver histochemistry) and microglial activation (Iba1). Significant neuropathology in PrV was evident at 2 and 7 days post-injury compared to sham. Iba1-labeled microglia showed swollen somata and thickened processes over 1 month post-injury. In contrast, the VIIN showed non-significant neuropathology and reduced labeling of activated Iba1 microglia over 1 month post-injury. Together with our previous data, neuropathology and neuroinflammation in the whisker somatosensory pathway may contribute to post-injury sensory sensitivity more than the motor pathway. Whether these findings are direct results of the mechanical injury or consequences of progressive degeneration remains to be determined.     

Null mutations of NT-3 and Bax affect trigeminal ganglion cell number but not brainstem barrelette pattern formation

Abstract

Trigeminal ganglion (TG) neurons innervate the grid-like array of whisker follicles on the face of the mouse. Central TG axons project to the trigeminal (V) brainstem nuclear complex, including the nucleus principalis (PrV) and the spinal subnucleus interpolaris (SpVi), where they innervate barrelettes that are organized in a pattern that recapitulates the whisker pattern on the face. Neurotrophin-3 (NT-3) supports a population of TG cells that supply slowly adapting mechanoreceptors in the whisker pad. We examined mice at embryonic day 17 (E17) and on the day of birth (P0) with null mutations of NT-3, Bax, a proapoptotic gene associated with naturally occurring cell death, and Bax/NT-3 double knockout (KO) mutants to determine if: (1) the number of TG cells would be reduced; (2) eliminating the Bax gene would rescue the NT-3-dependent neurons; and (3) the central projections of the rescued axons in the Bax/NT-3 double KO mice would fail to develop the barrelette patterns in the PrV and SpVi subnuclei. In mice at E17, NT-3^?/? mutants had 65% fewer TG neurons than found in age-matched wild-type (WT) mice, and at P0, the number was reduced by 55% (p?<?0.001 for both). Bax null mutant mice at E17 had 132% of the WT number of TG cells (p?<?0.001), although the numbers returned to WT levels by P0. Bax/NT-3 double KO mice at E17 had TG cell numbers equal to those seen in WT, but the double KO failed to retain WT TG neuron numbers in P0 mice (39% fewer cells; p?<?0.001). In all cases of reduced experimental neuron numbers, and in the E17 Bax^?/? mice with supernumerary cells, the barrelette patterns in the PrV and SpVi were normal. Only a slight qualitative reduction in overall barrelette field area and clarity of barrelettes were seen. These results suggest that NT-3 is not necessary for barrelette pattern formation in the brainstem.     

The Advantages of a Tapered Whisker

The role of facial vibrissae (whiskers) in the behavior of terrestrial mammals is principally as a supplement or substitute for short-distance vision. Each whisker in the array functions as a mechanical transducer, conveying forces applied along the shaft to mechanoreceptors in the follicle at the whisker base. Subsequent processing of mechanoreceptor output in the trigeminal nucleus and somatosensory cortex allows high accuracy discriminations of object distance, direction, and surface texture. The whiskers of terrestrial mammals are tapered and approximately circular in cross section. We characterize the taper of whiskers in nine mammal species, measure the mechanical deflection of isolated felid whiskers, and discuss the mechanics of a single whisker under static and oscillatory deflections. We argue that a tapered whisker provides some advantages for tactile perception (as compared to a hypothetical untapered whisker), and that this may explain why the taper has been preserved during the evolution of terrestrial mammals.     

The neurobiology and behavior of the American water shrew (Sorex palustris)

American water shrews (Sorex palustris) are aggressive predators that dive into streams and ponds to find prey at night. They do not use eyesight for capturing fish or for discriminating shapes. Instead they make use of vibrissae to detect and attack water movements generated by active prey and to detect the form of stationary prey. Tactile investigations are supplemented with underwater sniffing. This remarkable behavior consists of exhalation of air bubbles that spread onto objects and are then re-inhaled. Recordings for ultrasound both above and below water provide no evidence for echolocation or sonar, and presentation of electric fields and anatomical investigations provide no evidence for electroreception. Counts of myelinated fibers show by far the largest volume of sensory information comes from the trigeminal nerve compared to optic and cochlear nerves. This is in turn reflected in the organization of the water shrew’s neocortex, which contains two large somatosensory areas and much smaller visual and auditory areas. The shrew’s small brain with few cortical areas may allow exceptional speed in processing sensory information and producing motor output. Water shrews can accurately attack the source of a water disturbance in only 50 ms, perhaps outpacing any other mammalian predator.     

Activation of a wide-spread network of inhibitory neurons in barrel cortex

Abstract The one-to-one correspondence of whiskers to barrels in layer IV of rodent somatosensory cortex can be demonstrated by a precise match between columns of heavy 2-deoxyglucose (2DG) label in layer IV barrels and other layers which correspond to stimulated whiskers. While there is specificity of peripheral-to-central mapping, the extent to which integration and/or modulation are generated by circuitry within or interactions between the barrel-defined whisker columns is not clear. Following stimulation of selected whiskers, large cells at the layer IV-V boundary throughout the barrel field are heavily labeled by 2-deoxyglucose (2DG) at high resolution. Many of these cells are outside the barrel columns of the stimulated whiskers. Further, the number of cells labeled is not directly related to the number of activated barrel columns. These neurons are not labeled in animals anesthetized before 2DG injection and are not as heavily labeled in barrel fields of somnolent animals. Most of the heavily labeled neurons immunolabel for glutamate decarboxylase (GAD) and are presumed to be inhibitory, while a smaller number of labeled neurons, presumed to be excitatory, immunolabel for glutamate (Glu). Similar populations of large, heavily 2DG-labeled neurons are found in other cortical areas. These relatively few neurons are exceptionally active and may modulate integrative functions of cerebral cortex.     

Whisker plucking alters responses of rat trigeminal ganglion neurons

Whisker plucking in developing and adult rats provides a convenient method of temporarily altering tactile input for the purposes of studying experience-dependent plasticity in the somatosensory cortex. Yet, a comprehensive examination of the effect of whisker plucking on the response properties of whisker follicle-innervating trigeminal ganglion (NVg) neurons is lacking. We used extracellular single unit recordings to examine responses of NVg neurons to controlled whisker stimuli in three groups of animals: (1) rats whose whiskers were plucked from birth for 21 days; (2) rats whose whiskers were plucked once at 21 days of age; and (3) control animals. After at least 3 weeks of whisker re-growth, NVg neurons in plucked rats displayed normal, single whisker receptive fields and could be characterized as slowly (SA) or rapidly adapting (RA). The proportion of SA and RA neurons was unaffected by whisker plucking. Both SA and RA NVg neurons in plucked rats displayed normal response latencies and angular tuning but abnormally large responses to whisker movement onsets and offsets. SA neurons were affected to a greater extent than RA neurons. The effect of whisker plucking was more pronounced in animals whose whiskers were plucked repeatedly during development than in rats whose whiskers were plucked once. Individual neurons in plucked animals displayed abnormal periods of prolonged rhythmic firing following deflection onsets and aberrant bursts of activity during the plateau phase of the stimulus. These results indicate that whisker plucking exerts a long-term effect on responses of trigeminal ganglion neurons to peripheral stimulation.     

Whisker plucking alters responses of rat trigeminal ganglion neurons

Whisker plucking in developing and adult rats provides a convenient method of temporarily altering tactile input for the purposes of studying experience-dependent plasticity in the somatosensory cortex. Yet, a comprehensive examination of the effect of whisker plucking on the response properties of whisker follicle-innervating trigeminal ganglion (NVg) neurons is lacking. We used extracellular single unit recordings to examine responses of NVg neurons to controlled whisker stimuli in three groups of animals: (1) rats whose whiskers were plucked from birth for 21 days; (2) rats whose whiskers were plucked once at 21 days of age; and (3) control animals. After at least 3 weeks of whisker re-growth, NVg neurons in plucked rats displayed normal, single whisker receptive fields and could be characterized as slowly (SA) or rapidly adapting (RA). The proportion of SA and RA neurons was unaffected by whisker plucking. Both SA and RA NVg neurons in plucked rats displayed normal response latencies and angular tuning but abnormally large responses to whisker movement onsets and offsets. SA neurons were affected to a greater extent than RA neurons. The effect of whisker plucking was more pronounced in animals whose whiskers were plucked repeatedly during development than in rats whose whiskers were plucked once. Individual neurons in plucked animals displayed abnormal periods of prolonged rhythmic firing following deflection onsets and aberrant bursts of activity during the plateau phase of the stimulus. These results indicate that whisker plucking exerts a long-term effect on responses of trigeminal ganglion neurons to peripheral stimulation.     

The peripheral and central changes resulting from cutting or crushing the afferent nerve supply to the whiskers

In neonatal rats, crushing or cutting the infraorbital nerve, the sensory nerve supply to the whiskers, has been found to prevent cortical barrel formation. However, both procedures are followed by regeneration of one-third to one-half of the nerve fibres and reinnervation of the whiskers. By counting fibres in individual whisker follicle nerves, it has been shown that 29-67% (mean 45%) of the myelinated fibres regenerate to the whiskers after a crush compared to 24-56% (mean 39%) after a cut. Further differences between the crush and cut lesions were indicated by studies on the time course of regeneration. Counts of the regenerating fibres at various ages as well as recordings of cortical evoked potentials in normal, nerve-crushed and nerve-cut animals showed that recovery was 3-4 days earlier in the nerve-crushed, compared with the nerve-cut animals. In normal and nerve-crushed animals the evoked potential was first detectable 2-3 days after birth while the response after nerve cut could not be recorded until day 7. Even after 60 days the amplitude of responses on both crushed and cut pathways was only about one-third of normal, while the latency was prolonged (normal 5.8 +/- 0.25 ms, crush 6.5 +/- 0.26 ms, cut 7.7 +/- 0.67 ms). Central changes occurring as a result of nerve cut or crush have been studied by microelectrode recordings from the trigeminal nucleus (the first synaptic level) and the somatosensory cortex. These also indicate clearly the greater severity of the cut lesion. Thus, in crushed animals, all levels of the trigeminal nucleus as well as the cortex show only minor modifications. The whiskers occupy the same total area and responses from all whiskers are present at their normal sites. However, after nerve cut, the responses from both the trigeminal nucleus and cortex show clear abnormalities. The total whisker area is reduced with a concomitant expansion of responses from the nose, check, lower jaw, and whiskers by the eye and ear. In addition, only one-third to one-half of the whiskers give responses. The site of these abnormalities is localized to the trigeminal nucleus since all whiskers show innervation in the peripheral nerve. It is suggested that the longer recovery time as well as the reduced accuracy of reinnervation may contribute to the poorer central recovery after a nerve cut.     

胡须信息在大鼠双侧初级体感皮层间的传递路径

大鼠的初级体感皮层(primary somatosensory cortex,SⅠ)虽然只接受来自对侧胡须的上行输入,但仍可以被同侧胡须刺激所激活.解剖学研究发现,在两侧SⅠ皮层之间有两条传递胡须信息胼胝体通路:一条是类颗粒区(perigranular zone,PGZ)通路;另一条是异颗粒区(dysgranular zone,DZ)通路.然而,哪一条通路在传递胡须刺激信息的过程中起主要作用还不清楚.本研究使用电压敏感染料(voltage-sensitive dye,VSD)成像技术来观察胡须刺激时整个SⅠ的神经元群体活动的空间分布和时间特性.实验发现,对侧胡须刺激首先激活barrel(颗粒区,granular zone,GZ),然后以兴奋波的形式传播到胡须感觉区(sub-barrel field cortex,BFC)外侧的DZ.而与首先激活BFC的对侧胡须刺激不同,同侧胡须刺激首先激活SⅠ的DZ.所激发的皮层兴奋以波的形式传播并扩散至BFC.失活另一侧皮层可以抑制这种同侧反应.电刺激另一侧半球皮层与刺激同侧胡须类似,也首先激活成像侧DZ.我们的实验结果显示,胡须刺激激活对侧SⅠ,在经过胼胝体传导后,另一侧半球的DZ(同侧于被刺激的胡须)被激活.连接双侧皮层DZ区的胼胝体连接在SⅠ对同侧胡须刺激的反应中起了主导作用.     

Modeling the Emergence of Whisker Direction Maps in Rat Barrel Cortex

Based on measuring responses to rat whiskers as they are mechanically stimulated, one recent study suggests that barrel-related areas in layer 2/3 rat primary somatosensory cortex (S1) contain a pinwheel map of whisker motion directions. Because this map is reminiscent of topographic organization for visual direction in primary visual cortex (V1) of higher mammals, we asked whether the S1 pinwheels could be explained by an input-driven developmental process as is often suggested for V1. We developed a computational model to capture how whisker stimuli are conveyed to supragranular S1, and simulate lateral cortical interactions using an established self-organizing algorithm. Inputs to the model each represent the deflection of a subset of 25 whiskers as they are contacted by a moving stimulus object. The subset of deflected whiskers corresponds with the shape of the stimulus, and the deflection direction corresponds with the movement direction of the stimulus. If these two features of the inputs are correlated during the training of the model, a somatotopically aligned map of direction emerges for each whisker in S1. Predictions of the model that are immediately testable include (1) that somatotopic pinwheel maps of whisker direction exist in adult layer 2/3 barrel cortex for every large whisker on the rat''s face, even peripheral whiskers; and (2) in the adult, neurons with similar directional tuning are interconnected by a network of horizontal connections, spanning distances of many whisker representations. We also propose specific experiments for testing the predictions of the model by manipulating patterns of whisker inputs experienced during early development. The results suggest that similar intracortical mechanisms guide the development of primate V1 and rat S1.     

Optogenetic Patterning of Whisker-Barrel Cortical System in Transgenic Rat Expressing Channelrhodopsin-2

The rodent whisker-barrel system has been an ideal model for studying somatosensory representations in the cortex. However, it remains a challenge to experimentally stimulate whiskers with a given pattern under spatiotemporal precision. Recently the optogenetic manipulation of neuronal activity has made possible the analysis of the neuronal network with precise spatiotemporal resolution. Here we identified the selective expression of channelrhodopsin-2 (ChR2), an algal light-driven cation channel, in the large mechanoreceptive neurons in the trigeminal ganglion (TG) as well as their peripheral nerve endings innervating the whisker follicles of a transgenic rat. The spatiotemporal pattern of whisker irradiation thus produced a barrel-cortical response with a specific spatiotemporal pattern as evidenced by electrophysiological and functional MRI (fMRI) studies. Our methods of generating an optogenetic tactile pattern (OTP) can be expected to facilitate studies on how the spatiotemporal pattern of touch is represented in the somatosensory cortex, as Hubel and Wiesel did in the visual cortex.     

The sensory trigeminal system in birds: input, organization and effects of peripheral damage. A review.

The primary sensory trigeminal system in birds comprises the mesencephalic trigeminal nucleus and the trigeminal ganglion with projections to the principal sensory nucleus (PrV) and the descending tract with its subnuclei. Other cranial nerves can contribute to PrV and the descending system that together form the somatosensory system of the head. There is also a proprioceptive component. The somatosensory system comprises a component serving tactile sense and a nociceptive component. The former processes information from many mechanoreceptors in beak and tongue; both PrV and subnuclei of the descending system are involved. The nociceptive component consists of small ganglion cells projecting presumably to layers I and II of the caudal subnucleus of the descending trigeminal system and cervical dorsal horn; this is the only trigeminal region showing immunoreactivity for substance P. The effects of amputation of the tips of the beak of chickens (debeaking) are estimated by fiber counts in electron microscopic preparations of the trigeminal branches innervating that area, and by cell counts in Nissl stained sections of the trigeminal ganglion. Our data indicate that debeaking causes a loss of exteroceptive units, but not of nociceptive units. Comparison of sections stained for the presence of substance P (immunohistochemistry) did not reveal a long-term effect on the nociceptive system suggestive of the occurrence of chronic pain.     

去胡须对大鼠行为及桶状皮层的影响

目的:研究外周去胡须后大鼠行为及桶状皮层(barrel cortex,BC)的可塑性变化。方法:SD大鼠随机分组(n=4):正常对照(A组),出生后第2天去除双侧颊脂垫组(B组),出生后第2天去除右侧颊脂垫组(C组),出生后1～5d每天剪右侧胡须,从出生后第5天起不剪由其胡须自由生长组(D组)。出生后第30天时称体重,测量左侧D2胡须长度,观测行为学变化(如狭缝实验、自由探索行为和趋壁行为)。采用细胞色素氧化酶组织化学法研究barrel排列与发育情况。结果:A组能迅速辨别出正确狭缝并钻入,平均用时(5.6±2.3)s;B组大鼠只有当鼻尖碰到狭缝壁时才会钻入狭缝。C组大鼠当其右侧脸颊靠近狭缝时,不能辨别出狭缝,只有当其掉转身体,用左侧胡须探测时才可能迅速钻入正确的狭缝。D组的表现同C组,B、C、D组大鼠进入正确狭缝的所用时间均显著长于A组(P0.01,P0.05,P0.01)。去除双侧颊脂垫的大鼠其左趋壁时间、右趋壁时间以及总趋壁时间均较正常大鼠短。去除右侧颊脂垫组的大鼠右趋壁时间也显著短于正常(P0.05)。四组大鼠左侧D2胡须长度以及体重均无显著差异。从出生后第2天时一直剪除右侧胡须的小鼠在出生后第30天时发现其barrel变小,排列较混乱,barrel之间的界限不清,皮层细胞色素氧化酶(CO)反应的灰度明显变淡。结论:外周去传入不引起大鼠体重改变及残留胡须长度的代偿性改变,但可引起其趋触及探索行为方面的改变。外周去传入可导致barrel形状及排列的可塑性变化。     

In vitro formation of the Merkel cell‐neurite complex in embryonic mouse whiskers using organotypic co‐cultures

A Merkel cell‐neurite complex is a touch receptor composed of specialized epithelial cells named Merkel cells and peripheral sensory nerves in the skin. Merkel cells are found in touch‐sensitive skin components including whisker follicles. The nerve fibers that innervate Merkel cells of a whisker follicle extend from the maxillary branch of the trigeminal ganglion. Whiskers as a sensory organ attribute to the complicated architecture of the Merkel cell‐neurite complex, and therefore it is intriguing how the structure is formed. However, observing the dynamic process of the formation of a Merkel cell‐neurite complex in whiskers during embryonic development is still difficult. In this study, we tried to develop an organotypic co‐culture method of a whisker pad and a trigeminal ganglion explant to form the Merkel cell‐neurite complex in vitro. We initially developed two distinct culture methods of a single whisker row and a trigeminal ganglion explant, and then combined them. By dissecting and cultivating a single row from a whisker pad, the morphogenesis of whisker follicles could be observed under a microscope. After the co‐cultivation of the whisker row with a trigeminal ganglion explant, a Merkel cell‐neurite complex composed of Merkel cells, which were positive for both cytokeratin 8 and SOX2, Neurofilament‐H‐positive trigeminal nerve fibers and Schwann cells expressing Nestin, SOX2 and SOX10 was observed via immunohistochemical analyses. These results suggest that the process for the formation of a Merkel cell‐neurite complex can be observed under a microscope using our organotypic co‐culture method.     

In vivo imaging of neural circuit formation in the neonatal mouse barrel cortex

Higher brain function in mammals primarily relies on complex yet sophisticated neuronal circuits in the neocortex. In early developmental stages, neocortical circuits are coarse. Mostly postnatally, the circuits are reorganized to establish mature precise connectivity, in an activity-dependent manner. These connections underlie adult brain function. The rodent somatosensory cortex (barrel cortex) contains a barrel map in layer 4 (L4) and has been considered an ideal model for the study of postnatal neuronal circuit formation since the first report of barrels in 1970. Recently, two-photon microscopy has been used for analyses of neuronal circuit formation in the mammalian brain during early postnatal development. These studies have further highlighted the mouse barrel cortex as an ideal model. In particular, the unique dendritic projection pattern of barrel cortex L4 spiny stellate neurons (barrel neurons) is key for the precise one-to-one functional relationship between whiskers and barrels and thus an important target of studies. In this article, I will review the morphological aspects of postnatal development of neocortical circuits revealed by recent two-photon in vivo imaging studies of the mouse barrel cortex and other related works. The focus of this review will be on barrel neuron dendritic refinement during neonatal development.     

Whisker-related circuitry in the trigeminal nucleus principalis: Ultrastructure

Trigeminal (V) nucleus principalis (PrV) is the requisite brainstem nucleus in the whisker-to-barrel cortex model system that is widely used to reveal mechanisms of map formation and information processing. Yet, little is known of the actual PrV circuitry. In the ventral “barrelette” portion of the adult mouse PrV, relationships between V primary afferent terminals, thalamic-projecting PrV neurons, and gamma-aminobutyric acid (GABA)-ergic terminals were analyzed in the electron microscope. Primary afferents, thalamic-projecting cells, and GABAergic terminals were labeled, respectively, by Neurobiotin injections in the V ganglion, horseradish peroxidase injections in the thalamus, and postembedding immunogold histochemistry. Primary afferent terminals (Neurobiotin- and glutamate-immunoreactive) display asymmetric and multiple synapses predominantly upon the distal dendrites and spines of PrV cells that project to the thalamus. Primary afferents also synapse upon GABAergic terminals. GABAergic terminals display symmetric synapses onto primary afferent terminals, the somata and dendrites (distal, mostly) of thalamic-projecting neurons, and GABAergic dendrites. Thus, primary afferent inputs through the PrV are subject to pre- and postsynaptic GABAergic influences. As such, circuitry exists in PrV “barrelettes” for primary afferents to directly activate thalamic-projecting and inhibitory local circuit cells. The latter are synaptically associated with themselves, the primary afferents, and with the thalamic-projecting neurons. Thus, whisker-related primary afferent inputs through PrV projection neurons are pre- and postsynaptically modulated by local circuits.     

Functional asymmetries in the rodent barrel cortex

Neurophysiological and 2-deoxyglucose (2DG) studies of the rodent whisker barrel cortex have demonstrated asymmetries in its functional organization. To examine the possibility that the activity gradients observed in metabolic studies can be attributed to subtle rostral-caudal and dorsal-ventral asymmetries in electrophysiologically measured surround or cross-whisker inhibition, we compared 2DG results with predictions generated from quantitative single-cell receptive field data. Despite differences in the two experimental approaches, there is remarkable agreement between the findings. (1) The distribution of 2DG activity declines across the barrel cortex of the behaving animal from anteromedial barrels to posterolateral barrels, and is qualitatively and quantitatively similar to the values predicted from neurophysiology. (2) The strength of surround inhibition in barrel neurons predicts the twofold increase in activation of the C3 barrel following acute clipping of adjacent whiskers. And (3) within a cortical column, the decrease in metabolic activity associated with adjacent whisker stimulation is greatest in layer IV and least in the infragranular layers; this corresponds to the laminar distribution of inhibitory interactions observed electrophysiologically.     

Nerve growth factor increases stimulus-evoked metabolic activity in acetylcholine-depleted barrel cortex

Lesions of the basal forebrain deplete the neocortex of cholinergic fibers. Acetylcholine depletion in the somatosensory cortex of rats results in reduced stimulus-evoked activity in response to whisker stimulation. Previous studies demonstrate that embryonic basal forebrain transplants improve functional activity toward normal. It is not clear if the activity increase is due to cholinergic replacement or other factors present in the graft. In this study, we examined the possibility that nerve growth factor (NGF), a neurotrophin known as a survival factor and a specific protectant for cholinergic basal forebrain neurons, can preserve basal forebrain cells after a lesion and restore functional activity in the somatosensory cortex. We report that NGF alone is capable of restoring functional activity in the barrel cortex of animals with basal forebrain lesions, while vehicle injections of saline do not alter activity. Both high (10 mug) and low (5 mug) doses of NGF unilaterally injected into the lateral ventricle improved stimulus-evoked functional activity during bilateral whisker stimulation. The mechanism of NGF action is not clear since the restoration of functional activity in cortex was not accompanied by increased cholinergic activity as detected by acetylcholinesterase fiber staining. NGF may act directly on cortical neurons, although its site of action is not well defined.