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Roger L. Reep – One of the best experts on this subject based on the ideXlab platform.

  • The efficacy of the fluorescent conjugates of cholera toxin subunit B for multiple retrograde tract tracing in the central nervous system
    Brain Structure and Function, 2009
    Co-Authors: William L. Conte, Hiroaki Kamishina, Roger L. Reep
    Abstract:

    Cholera toxin subunit B (CTB) is a sensitive neuroanatomical tracer that generally transports retrogradely in the nervous system, and has been used extensively in brightfield microscopy. Recently, Alexa Fluor (AF) conjugates of CTB have been made available, which now allows multiple tracing with CTB. In this study, we examined the efficacy of these new AF-CTB conjugates when injected into the brain, and compared the results to our previous experiences using fluorescent 3k dextran amines. To test this, we injected AF 488 and AF 594 CTB into the anterior cingulate Cortex and the medial Agranular Cortex in the rat, and examined the retrograde transport to the lateral posterior nucleus of the thalamus. We found that CTB was very viscous but yet very sensitive: small injection sites revealed very intense and detailed retrograde labeling. Anterograde transport was seen only when tissue at the injection site was damaged. These findings suggest that AF-CTB is a very reliable and sensitive retrograde tracer, and should be the first choice retrograde tracer for experiments examining multiple pathways within the same brain.

  • Organization of the corticostriatal projection from rat medial Agranular Cortex to far dorsolateral striatum.
    Brain research, 2009
    Co-Authors: James V. Corwin, Roger L. Reep
    Abstract:

    The rat medial Agranular Cortex (AGm) projects bilaterally to the striatum, mainly to the dorsocentral striatum (DCS) and in a narrow band in the far dorsolateral striatum (FDLS). For the projection from AGm to DCS, axonal and synaptic densities are known to be two times greater in the ipsilateral versus contralateral DCS, producing a contralateral to ipsilateral ratio of 0.5. In the present study we wished to determine if this was also the case for the projection from AGm to FDLS. Injections of biotinylated dextran amine were made into AGm in normal rats, and unbiased sampling was used to quantify the density of axons and axonal varicosities present in the FDLS. Unlike the contra/ipsi ratio of 0.5 found in DCS, the FDLS exhibited a contra/ipsi ratio of 1.0 for both axonal and synaptic densities. While overall axonal densities were roughly equivalent in ipsilateral and contralateral FDLS, axonal density in the ipsilateral FDLS was uniform, whereas density in the contralateral FDLS increased from the medial edge of the band to its boundary at the external capsule. These differences in the bilateral projections of AGm to separate striatal regions raise questions regarding the populations of corticostriatal neurons in AGm that contribute to these projections.

  • Topography in the projections of lateral posterior thalamus with cingulate and medial Agranular Cortex in relation to circuitry for directed attention and neglect.
    Brain research, 2008
    Co-Authors: William L. Conte, James V. Corwin, Hiroaki Kamishina, Roger L. Reep
    Abstract:

    In the rat, the lateral posterior thalamic nucleus (LP) has reciprocal connections with areas of the Cortex and the striatum involved in directed attention and its dysfunctional counterpart, contralateral neglect. It has also been shown that the medial portion of the mediorostral part of LP (mLPMR) is of special interest because it has connections with the dorsocentral striatum, a key node in this circuitry. In the present study we used neuroanatomical tracers to map the specific connections and topography of LP with the anterior cingulate Cortex (ACC) and medial Agranular Cortex (AGm). We primarily used Alexa Fluor conjugates of the retrograde tracer cholera toxin subunit B, and injected two different colored conjugates into ACC and AGm in the same animal in order to directly compare the differential topography of the thalamocortical connections of mLPMR. The bidirectional tracer, dextran amine, was also used to examine anterograde corticothalamic projections of AGm and ACC. We found that mLPMR consists of two distinct groups of neurons, with the more dorsal group projecting to ACC and the more ventral group projecting to AGm. This is mirrored by a similar corticothalamic topography. These findings suggest that the ventral mLPMR is specifically associated with AGm and dorsocentral striatum, while dorsal mLPMR is associated with ACC. They also suggest that ACC may play a role in the circuitry for directed attention and contralateral neglect, as it is known to do in humans.

James V. Corwin – One of the best experts on this subject based on the ideXlab platform.

  • The time-dependent and persistent effects of amphetamine treatment upon recovery from hemispatial neglect in rats.
    Behavioural brain research, 2015
    Co-Authors: Miranda M. Brenneman, Michael J. Hylin, James V. Corwin
    Abstract:

    Abstract Neglect is a neuropsychological disorder characterized by the failure to report or respond to stimuli presented to the side of the body opposite a brain lesilesion and occurs in approximately 40% of right hemisphere strokes. The need for effective therapies to treat neglect in humans has led to the development of a rodent model. Unilateral destruction of medial Agranular Cortex (AGm), which is part of a cortical network for directed attention, produces severe multimodal neglect with deficits similar to those seen in humans. Amphetamines have previously been investigated for inducing plasticity and recovery of function following brain damage. Amphetamine treatment has been shown to produce recovery from visual, frontal, and sensorimotor Cortex damage in animals and this recovery may be the result of axonal growth originating from the opposite, unlesioned hemisphere. The purpose of this study was to investigate whether amphetamine treatment would induce recovery from neglect produced by unilateral AGm destruction, the time frame in which amphetamine must be administered in order to be effective, and the permanence of recovery following treatment. The results indicated that subjects injected with 2 mg/kg of d -amphetamine on days 0, 2, and 5 recovered in significantly fewer days than saline-treated controls, even when administration was delayed by 2 and 7 days. Additionally, these studies indicated that recovery persisted for at least 60 days suggesting that recovery is likely to be long term.

  • Organization of the corticostriatal projection from rat medial Agranular Cortex to far dorsolateral striatum.
    Brain research, 2009
    Co-Authors: James V. Corwin, Roger L. Reep
    Abstract:

    The rat medial Agranular Cortex (AGm) projects bilaterally to the striatum, mainly to the dorsocentral striatum (DCS) and in a narrow band in the far dorsolateral striatum (FDLS). For the projection from AGm to DCS, axonal and synaptic densities are known to be two times greater in the ipsilateral versus contralateral DCS, producing a contralateral to ipsilateral ratio of 0.5. In the present study we wished to determine if this was also the case for the projection from AGm to FDLS. Injections of biotinylated dextran amine were made into AGm in normal rats, and unbiased sampling was used to quantify the density of axons and axonal varicosities present in the FDLS. Unlike the contra/ipsi ratio of 0.5 found in DCS, the FDLS exhibited a contra/ipsi ratio of 1.0 for both axonal and synaptic densities. While overall axonal densities were roughly equivalent in ipsilateral and contralateral FDLS, axonal density in the ipsilateral FDLS was uniform, whereas density in the contralateral FDLS increased from the medial edge of the band to its boundary at the external capsule. These differences in the bilateral projections of AGm to separate striatal regions raise questions regarding the populations of corticostriatal neurons in AGm that contribute to these projections.

  • Topography in the projections of lateral posterior thalamus with cingulate and medial Agranular Cortex in relation to circuitry for directed attention and neglect.
    Brain research, 2008
    Co-Authors: William L. Conte, James V. Corwin, Hiroaki Kamishina, Roger L. Reep
    Abstract:

    In the rat, the lateral posterior thalamic nucleus (LP) has reciprocal connections with areas of the Cortex and the striatum involved in directed attention and its dysfunctional counterpart, contralateral neglect. It has also been shown that the medial portion of the mediorostral part of LP (mLPMR) is of special interest because it has connections with the dorsocentral striatum, a key node in this circuitry. In the present study we used neuroanatomical tracers to map the specific connections and topography of LP with the anterior cingulate Cortex (ACC) and medial Agranular Cortex (AGm). We primarily used Alexa Fluor conjugates of the retrograde tracer cholera toxin subunit B, and injected two different colored conjugates into ACC and AGm in the same animal in order to directly compare the differential topography of the thalamocortical connections of mLPMR. The bidirectional tracer, dextran amine, was also used to examine anterograde corticothalamic projections of AGm and ACC. We found that mLPMR consists of two distinct groups of neurons, with the more dorsal group projecting to ACC and the more ventral group projecting to AGm. This is mirrored by a similar corticothalamic topography. These findings suggest that the ventral mLPMR is specifically associated with AGm and dorsocentral striatum, while dorsal mLPMR is associated with ACC. They also suggest that ACC may play a role in the circuitry for directed attention and contralateral neglect, as it is known to do in humans.

J.v. Corwin – One of the best experts on this subject based on the ideXlab platform.

  • Overlap and interdigitation of cortical and thalamic afferents to dorsocentral striatum in the rat.
    Brain research, 2005
    Co-Authors: Joseph L. Cheatwood, J.v. Corwin, R L Reep
    Abstract:

    Dorsocentral striatum (DCS) is an associative region necessary for directed attention in rats. DCS is defined as the main region in which axons from ipsilateral medial Agranular Cortex (AGm) terminate within the striatum. In this double-labeling study, we placed a green axonal tracer in area AGm and a red one in an additional brain region. We examined the spatial relationship between terminals from area AGm and other portions of the cortical-basal ganglia-thalamic-cortical network involved in directed attention and its dysfunction, hemispatial neglect, in the rat. These include lateral Agranular Cortex (AGl), posterior parietal Cortex (PPC), ventrolateral orbital Cortex (VLO), and secondary visual Cortex (Oc2M). One important finding is the presence of a dense focus of labeled axons within DCS after injections in cortical area PPC or Oc2M. In these foci, axons from PPC or Oc2M extensively overlap and interdigitate with axons from cortical area AGm. Additionally, retrograde labeling of striatal neurons, along with double anterograde labeling, suggests that axons from cortical area AGm and AGl cross and possibly make contact with the dendritic processes of single medium spiny neurons. Axons from thalamic nucleus LP were observed to form a dense band dorsal to DCS which is similar to that seen following PPC injections, and a significant number of LP axons were also observed within DCS. Projections from thalamic nucleus VL are present in the dense dorsolateral AGm band that abuts the external capsule, are densest in the dorsolateral striatum, and were not observed in DCS. These results extend previous findings that DCS receives input from diverse cortical areas and thalamic nuclei which are themselves interconnected.

  • Topographic organization of the striatal and thalamic connections of rat medial Agranular Cortex.
    Brain research, 1999
    Co-Authors: R L Reep, J.v. Corwin
    Abstract:

    The rostral and caudal portions of rat medial Agranular Cortex (AGm) play different functional roles. To refine the anatomical framework for understanding these differences, axonal tracers were used to map the topography of the connections of AGm with the striatum and thalamus. The striatal projections follow mediolateral and rostrocaudal gradients that correspond to the locations of the neurons of origin within AGm. Projections from rostral AGm are widespread and dense rostrally, then coalesce into a circumscribed dorsocentral region at the level of the pre-commissural septal nuclei. Projections from mid and caudal AGm are less widespread and less dense, and are focused more caudally. Striatal projections from the adjacent anterior cingulate and lateral Agranular areas overlap those of AGm but are concentrated more medially and laterally, respectively. Thalamic connections of AGm are organized so that more caudal portions of AGm have connections with progressively more lateral and caudal regions of the thalamus, and the full extent of AGm is connected with the ventrolateral (VL) nucleus. Rostral AGm is interconnected with the lateral portion of the mediodorsal nucleus (MD1), VL, and the central lateral (CL), paracentral (PC), central medial, rhomboid and ventromedial nuclei. Caudal AGm has robust connections with VL, the posterior, lateral posterior and lateral dorsal nuclei, but little or none with MD1, CL/PC and VM. These differences in the subcortical connections of rostral and caudal AGm parallel their known differences in corticocortical connections, and represent another basis for experimental explorations of the functional roles of these cortical territories.

  • Apomorphine produces an acute dose-dependent therapeutic effect on neglect produced by unilateral destruction of the posterior parietal Cortex in rats.
    Behavioural brain research, 1996
    Co-Authors: J.v. Corwin, K J Burcham, G I Hix
    Abstract:

    The neglect syndrome is a complex and devastating neurological disorder typically induced by unilateral destruction of one of three regions of the neoCortex: the inferior parietal lobule, the dorsolateral prefrontal Cortex or the cingulate Cortex. Previous studies of neglect using a rodent model have indicated that disruption of dopaminergic mechanisms may underlie neglect. However, the pharmacological results were obtained using a rodent prefrontal model of the syndrome (medial Agranular Cortex), whereas the majority of cases of neglect in humans are produced by unilateral destruction of the posterior parietal Cortex (inferior parietal lobule). The present study examined the effects of administration of the dopamine receptor agonist apomorphine on neglect induced by unilateral destruction of the posterior parietal Cortex (PPC) in rats. The results indicated that administration of apomorphine produced a significant dose-dependent decrease in the severity of neglect. The results support the contention that neglect induced by cortical damage may be produced by a disruption of dopaminergic mechanisms, and that the PPC may be one component of a cortical system for directed attention.

K J Burcham – One of the best experts on this subject based on the ideXlab platform.

  • Unilateral destruction of the medial Agranular cortical projection zone in the dorsocentral striatum produces severe neglect in rats
    Psychobiology, 2000
    Co-Authors: Thomas M. Vleet, K J Burcham, James V. Corwin, Roger L. Reep
    Abstract:

    Physiological studies have indicated that neglect and recovery from neglect induced by unilateral lesions of the medial Agranular Cortex (AGm) in rats is correlated with reductions of metabolic activity and plastic changes in glutamate receptors in the dorsolateral quadrant of the striatum. The dorsolateral quadrant of the striatum encompasses the dorsocentral striatum (DCS), the projection zone of AGm efferents. Although these changes in function in the dorsolateral striatum are correlated with neglect and behavioral recovery, direct evidence for the role of this region is lacking. In the present study, we examined the behavioral effects of unilateral destruction of the DCS on neglect, as assessed by orientation to visual, auditory, and tactile stimulation. Subjects received a unilateral N -methyl- d -aspartate lesion of the DCS, a control lesion in a laterally adjacent site in the striatum, or an injection of vehicle into the DCS. The subjects were tested for neglect three times per week for 3 weeks by rating the magnitude of orientation to visual, tactile, and auditory stimstimulation. The results indicate that the DCS group demonstrated significantly more severe neglect than did the lesion control group or the vehicle controls. The results suggest that the DCS is part of a system for appropriate orientation to sensory stimuli in rats and that the DCS may play a pivotal role in behavioral recovery from neglect produced by AGm lesions.

  • Effects of delay and duration of light deprivation on recovery of function from neglect induced by unilateral medial Agranular prefrontal Cortex lesions in rats
    Psychobiology, 1998
    Co-Authors: K J Burcham, James V. Corwin
    Abstract:

    Forty-eight hours of postoperation light deprivation (LD) has been found to produce complete and permanent behavioral recovery of function from neglect induced by unilateral lesions of medial Agranular Cortex (AGm) in rats. The two experiments in the present study parametrically examined the postoperation delay prior to LD and the duration of LD necessary to produce recovery from severe neglect. Subjects in both experiments received unilateral AGm lesions and were tested for the degree of neglect of visual, tactile, and auditory stimuli prior to and after experiencing LD. The results of the study of delay of LD indicated that LD administered 4 h postsurgery produced dramatic immediate recovery from severe neglect, and the recovery lasted for the duration of behavioral testing (3 weeks) following LD. The longer delay groups (52 and 100 h) and the no-manipulation controls did not demonstrate behavioral recovery. The 28-h delay group demonstrated an intermediate effect following LD. The results of the study of duration of LD indicated that the therapeutic effect of LD was duration dependent. Forty-eight hours of LD produced a significant reduction in the severity of neglect, but shorter durations (4 and 24 h) did not. The results of the present study indicate that a critical postoperative period exists in which LD must be initiated in order to produce recovery from severe neglect and that LD has to be administered for a period of at least 24 h to produce any evidence of recovery of function. These findings may have clinical implications for the treatment of neglect in humans.

  • Light deprivation produces a therapeutic effect on neglect induced by unilateral destruction of the posterior parietal Cortex in rats
    Behavioural brain research, 1998
    Co-Authors: K J Burcham, James V. Corwin, Thomas M. Van Vleet
    Abstract:

    Light deprivation has been found to produce accelerated recovery from severe multimodal neglect induced by unilateral destruction of medial Agranular Cortex, the rat analog of area 8 in humans. However, neglect in humans is most often produced by destruction of the parietal association Cortex. Therefore, the present study examined whether light deprivation would produce accelerated recovery from severe multimodal neglect induced by unilateral destruction of the rodent analog of the parietal association Cortex. Subjects received unilateral parietal association Cortex lesions, and 4 h after surgery were tested for neglect of visual, tactile, and auditory stimuli. If severe neglect was obtained, subjects experienced either light deprivation, constant light, or a 12:12 light/dark cycle for 48 h. The results indicated that, relative to the other groups, the light deprivation group demonstrated significant accelerated recovery from neglect. Recovery was evident on the first post-light deprivation behavioral test, and was maintained for the 3 weeks of behavioral testing. The results provide further support for the therapeutic effects of light deprivation on neglect induced by cortical lesions when light deprivation is administered in the immediate postoperative period.

Joseph L. Cheatwood – One of the best experts on this subject based on the ideXlab platform.

  • Quantification of synaptic density in corticostriatal projections from rat medial Agranular Cortex.
    Brain research, 2008
    Co-Authors: Roger L. Reep, Joseph L. Cheatwood, Gwendolyn L Kartje, James V. Corwin, Anis Khusro Mir
    Abstract:

    Medial Agranular Cortex (AGm) has a prominent bilateral projection to the dorsocentral striatum (DCS). We wished to develop a normal baseline by which to assess neuronal plasticity in this corticostriatal system in rats with neglect resulting from a unilateral lesion in AGm, followed by treatment with agents that promote sprouting and functional recovery in other systems. Injections of biotinylated dextran amine were made into AGm in normal rats, and unbiased sampling was used to quantify the density of axons and axonal varicosities present in DCS (the latter represent presynaptic profiles). Labeling density in contralateral DCS is approximately half of that seen in ipsilateral DCS (this ratio is 0.50 for axons, 0.55 for varicosities). The ratio of varicosities is stable over a greater than seven-fold range of absolute densities. There is no consistent relationship between the absolute density of axons and axon varicosities; however, the ratio measures are strongly correlated. We conclude that changes in the contralateral/ipsilateral ratio of axon density after experimental treatments do reflect changes in synaptic density, but axon varicosities are likely to be the most sensitive anatomical parameter by which to assess plasticity at the light microscopic level.

  • Nogo-A inhibition induces recovery from neglect in rats.
    Behavioural Brain Research, 2007
    Co-Authors: Miranda M. Brenneman, Roger L. Reep, James V. Corwin, Steven J. Wagner, Joseph L. Cheatwood, Scott A. Heldt, Gwendolyn L Kartje, Martin E. Schwab
    Abstract:

    Neglect is a complex human cognitive spatial disorder typically induced by damage to prefrontal or posterior parietal association cortices. Behavioral treatments for neglect rarely generalize outside of the therapeutic context or across tasks within the same therapeutic context. Recovery, when it occurs, is spontaneous over the course of weeks to months, but often it is incomplete. A number of studies have indicated that anti-Nogo-A antibodies can be used to enhance plasticity and behavioral recovery following damage to motor Cortex, and spinal cord. In the present studies the anti-Nogo-A antibodies IN-1, 7B12, or 11C7 were applied intraventricularly to adult rats demonstrating severe neglect produced by unilateral medial Agranular Cortex lesions in rats. The three separate anti-Nogo-A antibody groups were treated immediately following the medial Agranular Cortex lesions. Each of the three antibodies induced dramatic significant behavioral recovery from neglect relative to controls. Severing the corpus callosum to destroy inputs from the contralesional hemisphere resulted in reinstatement of severe neglect, pointing to a possible role of interhemispheric mechanisms in behavioral recovery from neglect.

  • Overlap and interdigitation of cortical and thalamic afferents to dorsocentral striatum in the rat.
    Brain research, 2005
    Co-Authors: Joseph L. Cheatwood, J.v. Corwin, R L Reep
    Abstract:

    Dorsocentral striatum (DCS) is an associative region necessary for directed attention in rats. DCS is defined as the main region in which axons from ipsilateral medial Agranular Cortex (AGm) terminate within the striatum. In this double-labeling study, we placed a green axonal tracer in area AGm and a red one in an additional brain region. We examined the spatial relationship between terminals from area AGm and other portions of the cortical-basal ganglia-thalamic-cortical network involved in directed attention and its dysfunction, hemispatial neglect, in the rat. These include lateral Agranular Cortex (AGl), posterior parietal Cortex (PPC), ventrolateral orbital Cortex (VLO), and secondary visual Cortex (Oc2M). One important finding is the presence of a dense focus of labeled axons within DCS after injections in cortical area PPC or Oc2M. In these foci, axons from PPC or Oc2M extensively overlap and interdigitate with axons from cortical area AGm. Additionally, retrograde labeling of striatal neurons, along with double anterograde labeling, suggests that axons from cortical area AGm and AGl cross and possibly make contact with the dendritic processes of single medium spiny neurons. Axons from thalamic nucleus LP were observed to form a dense band dorsal to DCS which is similar to that seen following PPC injections, and a significant number of LP axons were also observed within DCS. Projections from thalamic nucleus VL are present in the dense dorsolateral AGm band that abuts the external capsule, are densest in the dorsolateral striatum, and were not observed in DCS. These results extend previous findings that DCS receives input from diverse cortical areas and thalamic nuclei which are themselves interconnected.