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F F Ebner

Publications and source records attributed to F F Ebner.

At least 37 records · Page 2Linked to original sources
PubMed1994

Laminar comparison of somatosensory cortical plasticity.

During tactile learning there is a transformation in the way the primary somatosensory cortex integrates, represents, and distributes information from the skin. To define this transformation, the site of earliest modification has been identified in rat somatosensory cortex after a change in sensory experience. Afferent activity was manipulated by clipping all except two whiskers on one side of the snout ("whisker pairing"), and the receptive fields of neurons at different cortical depths were mapped 24 hours later. Neurons in layer IV, the target of the primary thalamic pathway, were unaltered, whereas neurons located above and below layer IV showed significant changes. These changes were similar to those that occur in layer IV after longer periods of whisker pairing. The findings support the hypothesis that the layers of cortex contribute differently to plasticity. Neurons in the supragranular and infragranular layers respond rapidly to changes in sensory experience and may contribute to subsequent modification in layer IV.

Action Potentials↗
PubMed1994

Dynamic synaptic modification threshold: computational model of experience-dependent plasticity in adult rat barrel cortex.

Previous electrophysiological experiments have documented the response of neurons in the adult rat somatic sensory ("barrel") cortex to whisker movement after normal experience and after periods of experience with all but two whiskers trimmed close to the face (whisker "pairing"). To better understand how the barrel cortex adapts to changes in the flow of sensory activity, we have developed a computational model of a single representative barrel cell based on the Bienenstock, Cooper, and Munro (BCM) theory of synaptic plasticity. The hallmark of the BCM theory is the dynamic synaptic modification threshold, theta M, which dictates whether a neuron's activity at any given instant will lead to strengthening or weakening of the synapses impinging on it. The threshold theta M is proportional to the neuron's activity averaged over some recent past. Whisker pairing was simulated by setting input activities of the cell to the noise level, except for two inputs that represented untrimmed whiskers. Initially low levels of cell activity, resulting from whisker trimming, led to low values for theta M. As certain synaptic weights potentiated, due to the activity of the paired inputs, the values of theta M increased and after some time their mean reached an asymptotic value. This saturation of theta M led to the depression of some inputs that were originally potentiated. The changes in cell response generated by the model replicated those observed in in vivo experiments. Previously, the BCM theory has explained salient features of developmental experience-dependent plasticity in kitten visual cortex. Our results suggest that the idea of a dynamic synaptic modification threshold, theta M, is general enough to explain plasticity in different species, in different sensory systems, and at different stages of brain maturity.

Animals↗
PubMed1994

The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus. I. Assessment of receptive field changes following thalamic reticular nucleus lesions.

1. Changes in the receptive field (RF) properties of thalamic VPM neurons were assessed quantitatively using single-unit recording techniques following a selective excitotoxic lesion of the ipsilateral thalamic reticular nucleus (TRN). The response profiles to controlled deflections of the contralateral vibrissae were obtained from 97 VPM neurons in normal and 102 VPM neurons in TRN-lesioned animals. 2. Histological signs of TRN lesions were detectable in Nissl-stained sections as early as 20 h after the release of kainic acid into TRN. 3. The average RF size of VPM neurons in normal animals was 2.39 +/- 0.18 whiskers (mean +/- SE). Immediately after the lesion of TRN, the average RF size in VPM was enlarged significantly and remained expanded for as long as 1 mo after the destruction of TRN (7.64 +/- 0.47 whiskers, P < 0.001). 4. Subsequent lesions of trigeminal subnucleus interpolaris (SpVi) in TRN-lesioned animals produced a marked reduction in the RF size of VPM neurons. The average VPM RF size for TRN/SpVi lesioned animals was 2.14 +/- 0.64 whiskers. 5. The loss of inhibition from TRN increased the average response probability and magnitude to the center RF whisker by 38 and 34%, respectively. The response probability and magnitude of the surround RF whiskers increased by 64 and 69%, respectively. The average response latencies to the center and surround RF whiskers were significantly longer after the lesion of TRN; subsequent lesions of SpVi in TRN-lesioned cases reduced the average response latencies of VPM neurons to those seen in normal animals. 6. The RF of VPM neurons in both normal and TRN lesioned cases displayed a strong anterior-posterior ("row") preference. Immediately adjacent anterior-posterior whiskers were twice as likely to elicit a response in VPM than immediately adjacent dorsal-ventral whiskers. 7. VPM units were tested for a preferential response to whisker movement in one of four directions (up, down, backward, and forward). The majority of the neurons in both normal and TRN-lesioned cases showed direction-selective responses, mostly in the up direction. Thus gamma-aminobutyric acid (GABA)-mediated inhibition in rat VPM does not appear to be responsible for direction selectivity of VPM neurons. 8. Virtually all neurons in rat VPM after TRN lesions displayed responses that were sustained for the duration of the stimulus (25.5% in normal vs. 88.2% in TRN-lesioned cases). VPM units showing sustained (tonic) responses maintained a high rate of spontaneous activity and, on average, responded to 2-3 times more whiskers than phasically responding units.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus. II. Differential effects of GABAA and GABAB receptor antagonists on responses of VPM neurons.

1. Changes in the response properties of 106 ventral posterior medial (VPM) units were assessed after iontophoretic blockade of gamma-aminobutyric acid-A or -B (GABAA or GABAB) receptor-mediated inhibition using bicuculline methiodide (BIC) or 2-hydroxy-saclofen (2-OH-S), respectively. 2. The iontophoretic administration of either BIC or 2-OH-S did not alter significantly the average spontaneous firing rate of VPM neurons for current intensities between 40 and 80 nA. The presence of 10 mM 2-OH-S (60 nA) was effective in completely reversing the depressant effects of the selective GABAB receptor agonist, baclofen, on the spontaneous activity of VPM neurons. 3. The effect of BIC on whisker-evoked responses was a preferential enhancement in the responses elicited by the whisker giving rise to the highest probability response (center receptive field whisker or CRF). The effect of 2-OH-S (40-80 nA iontophoretic currents) was to increase the responsiveness of VPM neurons to the stimulation of whiskers in all parts of the receptive field (RF), although its influence was much more pronounced in the peripheral areas of the RF (surround receptive field whisker or SRF). This preferential enhancement of SRF-whisker responses after the blockade of GABAB receptor-mediated inhibition resulted in a 2.3-fold increase in the average RF size of VPM neurons; no statistically significant increases in the size of the RF were seen in the presence of BIC. 4. The primary influence of BIC and, to a lesser degree, 2-OH-S was to prolong the response duration of VPM neurons to CRF whisker stimulation. Under our recording conditions, approximately 25% of VPM neurons in normal animals responded with sustained discharges. In the presence of BIC and 2-OH-S, the percent of VPM units that could be classified as tonically responding increased to 82% and 67%, respectively. 5. The proportion of VPM neurons that was selective to the deflection of whiskers in a particular direction (87%) was not altered in the presence of BIC or 2-OH-S. 6. BIC was effective in antagonizing GABA-mediated inhibition within the first 40 ms of a stimulus; BIC was completely ineffective in reversing a late suppression seen between 80 and 140 ms. In contrast, no statistically significant changes in the initial GABA-mediated inhibition were seen in the presence of 2-OH-S, but 2-OH-S was partially effective in antagonizing the late suppression of responses in VPM neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1994

An innocuous bias in whisker use in adult rats modifies receptive fields of barrel cortex neurons.

The effect of innocuously biasing the flow of sensory activity from the whiskers for periods of 3-30 d in awake, behaving adult rats on the receptive field organization of rat SI barrel cortex neurons was studied. One pair of adjacent whiskers, D2 and either D1 or D3, remained intact unilaterally (whisker pairing), all others being trimmed throughout the period of altered sensation. Receptive fields of single cells in the contralateral D2 barrel were analyzed under urethane anesthesia by peristimulus time histogram (PSTH) and latency histogram analysis after 3, 7-10, and 30 d of pairing and compared with controls, testing all whiskers cut to the same length. Response magnitudes to surround receptive field in-row whiskers D1 and D3 were not significantly different for control animals. The same was found for surround in-arc whiskers C2 and E2. However, after 3 d of whisker pairing a profound bias occurred in response to the paired D-row surround whisker relative to the opposite trimmed surround D-row whisker and to the C2 and E2 whiskers. This bias increased with the duration of pairing, regardless of which surround whisker (D1 or D3) was paired with D2. For all three periods of pairing the mean response to the paired surround whisker was increased relative to controls, but peaked at 7-10 d. Response to the principal center-receptive (D2) whisker was increased for the 3 and 7-10 d groups and then decreased at 30 d. Responses to trimmed arc surround whiskers (C2 and E2) were decreased in proportion to the duration of changed experience. Analysis of PSTH data showed that earliest discharges (5-10 msec poststimulus) to the D2 whisker increased progressively in magnitude with duration of pairing. For the paired surround whisker similar early discharges newly appeared after 30 d of pairing. At 3 and 7-10 d of pairing, increases in response to paired whiskers and decreases to cut surround whiskers were confined to late portions of the PSTH (10-100 msec poststimulus). Changes at 3-10 d can be attributed to alterations in intracortical synaptic relay between barrels. Longer-term changes in response to both paired whisker inputs (30 d) largely appear to reflect increases in thalamocortical synaptic efficacy. Our findings suggest that novel innocuous somatosensory experiences produce changes in the receptive field configuration of cortical cells that are consistent with Hebbian theories of experience-dependent potentiation and weakening of synaptic efficacy within SI neocortical circuitry, for correlated and uncorrelated sensory inputs, respectively.

Animals↗
PubMed1993

Experience-dependent plasticity in adult rat barrel cortex.

This study tested the hypothesis that the receptive fields (RFs) of neurons in the adult sensory cortex are shaped by the recent history of sensory experience. Sensory experience was altered by a brief period of "whisker pairing": whiskers D2 and either D1 or D3 were left intact, while all other whiskers on the right side of the face were trimmed close to the fur. The animals were anesthetized 64-66 h later and the responses of single neurons in contralateral cortical barrel D2 to stimulation of whisker D2 (the center RF) and the four neighboring whiskers (D1, D3, C2, and E2; the excitatory surround RF) were measured. Data from 79 cells in four rats with whiskers paired were compared to data from 52 cells in four rats with untrimmed whiskers (control cases). During the period of whisker pairing, the RFs of cells in barrel D2 changed in three ways: (i) the response to the center RF, whisker D2, increased by 39%, (ii) the response to the paired surround RF whisker increased by 85-100%, and (iii) the response to all clipped (unpaired) surround RF whiskers decreased by 9-42%. In the control condition, the response of barrel D2 cells to the two neighboring whiskers, D1 and D3, was equal. After whisker pairing, the response to the paired neighbor of D2 was more than twice as large as the response to the cut neighbor of D2. These findings indicate that a brief change in the pattern of sensory activity can alter the configuration of cortical RFs, even in adult animals.

Animals↗
PubMed1992

Somatic sensory responses in the rostral sector of the posterior group (POm) and in the ventral posterior medial nucleus (VPM) of the rat thalamus: dependence on the barrel field cortex.

The projection from the whiskers of the rat to the S-I (barrel) cortex is segregated into two separate pathways--a lemniscal pathway relayed by the ventral posterior medial nucleus (VPM) to cortical barrels, and a paralemniscal pathway relayed by the rostral sector of the posterior complex (POm) to the matrix between, above, and below barrels. Before investigating how the barrel cortex integrates these sensory pathways, it is important to learn more about the influence of the various inputs to the two thalamic nuclei. Based on the greater density of descending versus ascending projections to POm, it seemed likely that corticofugal inputs play an important role in the sensory activity of POm. To test this, the responses of POm and VPM cells to sensory stimuli were measured before, during, and after suppression of the S-I cortex. S-I was suppressed by application of magnesium or by cooling; the status of the barrel cortex was assessed continuously by an electrocorticogram. All VPM cells (n = 8) responded vigorously to whisker movement even when the barrel cortex was profoundly depressed. In contrast, all POm cells (n = 9) failed to respond to whisker movement once the barrel cortex became depressed, typically about 25 minutes after the start of cortical cooling or magnesium application. POm cells regained responsiveness about 30 minutes after the cessation of cortical cooling or the washoff of magnesium. These findings indicate that the transmission of sensory information through the lemniscal pathway occurs independently of the state of cortex, whereas transmission through the paralemniscal pathway depends upon the state of the cortex itself.

Animals↗
PubMed1992

Somatic sensory responses in the rostral sector of the posterior group (POm) and in the ventral posterior medial nucleus (VPM) of the rat thalamus.

The rodent barrel field cortex integrates somatosensory information from two separate thalamic nuclei, the ventral posterior medial nucleus (VPM) and the rostral sector of the posterior complex (POm). This paper compares the sensory responses of POm and VPM cells in urethane-anesthetized rats as a first step in determining how cortex integrates multiple sensory pathways. A complete representation of the contralateral body surface was identified in POm. Trigeminal receptive fields (RFs) of POm and VPM cells were mapped by computer-controlled displacement of individual whiskers; responses were quantified by using peristimulus time histograms. Average RF size was similar in POm (5.1 whiskers) and VPM (4.4 whiskers), but evoked responses in the two nuclei differed significantly according to all other measures. VPM cells were maximally responsive to one single whisker--the "center RF." Stimulating this whisker evoked, on average, a response of 1.4 spikes/stimulus at a latency of 7 ms; surrounding whiskers evoked responses of less than 1 spike/stimulus at latencies of greater than 8 ms. In contrast, POm cells were nearly equally responsive to several whiskers. Quantitative criteria allowed us to designate a single whisker as the "center RF" and stimulating this whisker evoked, on average, a response of 0.5 spikes/stimulus at a latency of 19 ms. VPM cells, but not POm cells, were able to "follow" repeated whisker deflection at greater than 5 Hz. We conclude that, when a single whisker is deflected, VPM activates the related cortical barrel-column at short latency--before the onset of activity in POm. The timing of activation could allow POm cells to modulate the spread of activity between cortical columns.

Animals↗
PubMed1992

Induction of high frequency activity in the somatosensory thalamus of rats in vivo results in long-term potentiation of responses in SI cortex.

Extracellular single-unit techniques were employed to record unitary activity simultaneously from the thalamic ventral posterior medial (VPM) nucleus and the ipsilateral primary somatosensory cortex of adult rats. Cross-correlation analysis triggered by the spontaneous firing of thalamocortical relay neurons in VPM and the discharge of layer IV neurons in the corresponding ipsilateral cortical barrel indicated that the paired-units included in this study were strongly correlated in their activity. The baseline responses of highly correlated cortical/thalamic pairs to a 10 ms deflection of a vibrissa on the contralateral side were measured using poststimulus time histograms. After establishing the baseline response, high frequency activity in VPM was induced in one of two ways: i) direct electrical stimulation of thalamic neurons or ii) whisker stimulation in the presence of bicuculline methiodide (BIC) released near the thalamic neurons. Both methods resulted in a conditioning stimulus (CS) paradigm consisting of "burst" of high-frequency activity (50-100 Hz) with an inter-burst interval of 150 ms (approximately 7 Hz). Almost immediately following the presentation of the CS, the response of layer IV cortical neurons to vibrissa stimulation increased by 37-62% over baseline values, which was maintained after the effects of BIC had worn off in VPM. This enhancement in the response of the cortical neurons was not accompanied by a concomitant increase in the thalamic responses. Thus, these results strongly suggest that the potentiation first occurred at the thalamocortical synapse.

Animals↗
PubMed1991

Horizontal long-term potentiation of responses in rat somatosensory cortex.

The search for mechanisms in neocortex that change synaptic efficacy and produce associative learning through activity-dependent processes has focused on the role of glutamate receptors of the N-methyl-D-aspartate (NMDA) type. NMDA receptor activation is necessary for the induction of long-term potentiation (LTP) in hippocampus and in neocortex. The effect of NMDA receptor activation is modulated in several ways, including Mg2+ block of the NMDA-dependent channel which prevents Ca2+ entry until neurons become partially depolarized. We report that when NMDA receptor activation is facilitated by lowering the extracellular [Mg2+] in the bathing medium, a low-frequency train presented in layer VI induces potentiated responses throughout a wide horizontal extent of layer II/III in neocortical slices. The response amplitudes potentiated by 34-200% over baseline values depending on the intensity of the repetitive conditioning stimulus and the distance of the recording site from the stimulus. At the same time that pre-existing evoked responses were potentiated, horizontal spread of activity in layer II/III was facilitated resulting in responses appearing at sites more than 1 mm from the stimulus. This enhanced transmission of responses persisted for greater than 2 h, and its induction was prevented by selective NMDA receptor antagonists. The results show that the horizontal spread of activity can be increased by altering the conditions of the stimulus presentation. We conclude that the mechanisms supporting LTP could determine the area of neocortex that is activated by a sensory input.

Animals↗
PubMed1990

Thalamic retrograde degeneration following cortical injury: an excitotoxic process?

Traumatic or stroke-like injuries of the cerebral cortex result in the rapid retrograde degeneration of thalamic relay neurons that project to the damaged area. Although this phenomenon has been well documented, neither the basis for the relay neuron's extreme sensitivity to axotomy nor the mechanisms involved in the degenerative process have been clearly identified. Physiological and biochemical studies of the thalamic response to cortical ablation indicate that pathological overexcitation might contribute to the degenerative process. The responses of thalamic projection neurons, protoplasmic astrocytes, and inhibitory thalamic reticular neurons in adult mice were examined from one to 120 days following ablation of the somatosensory cortex as part of an investigation of the role of excitotoxicity in thalamic retrograde degeneration. The responses of thalamic neurons to cortical ablation were compared with those produced by intracortical injection of the convulsant excitotoxin kainic acid, since the degeneration of neurons in connected brain structures distant to the site of kainic acid injection is also thought to occur via an excitotoxic mechanism. Within two days after either type of cortical injury, protoplasmic astrocytes in affected regions of the thalamic ventrobasal complex and the medial division of the posterior thalamic nuclei became reactive and expressed increased levels of immunohistochemically detectable glial fibrillary acidic protein. Within the affected regions of the ventrobasal complex an increased intensity of puncta positive for glutamate decarboxylase immunoreactivity, presumably due to an increase in its content within the terminals of the reciprocally interconnected thalamic reticular neurons, was also evident. These immunohistochemically detectable alterations in the milieu of the damaged thalamic neurons preceded the disappearance of the affected relay neurons by at least two days following cortical ablation and by seven to 10 days following intracortical kainic acid injection. Regions of the thalamus containing reactive astrocytes corresponded very closely to the regions undergoing retrograde degeneration. Protoplasmic astrocytes in these areas remained intensely reactive up to 60 days after cortical injury. Levels of glutamate decarboxylase were only transiently elevated in the degenerating regions of the ventrobasal complex following cortical ablation and returned to normal by 14 days. Increased glutamate decarboxylase immunoreactivity was transiently seen through the entire ventrobasal complex following intracortical kainic acid injection but was markedly more intense in degenerating regions. These patterns of labeling did not return to normal until 50 days after intracortical kainic acid injection, well after the death of the relay neurons. Cortical ablation and intracortical kainic acid injection produce similar alterations in thalamic neuronal and glial populations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Intracortical processes regulating the integration of sensory information.

The mechanisms that link sensory inputs in spatially separated regions of cortex can be elucidated by analyzing the mechanisms that generate receptive field properties in cortical neurons under conditions that mimic the waking state; a state when learning, memory and the modification of synaptic strength can be most readily demonstrated. Important advances in understanding receptive field mechanisms in sensory cortex have arisen from studying the precise relationship between the mystacial vibrissae or "whiskers" and their neural representation in separate cortical domains or "barrels". The anatomical precision of whisker projections to barrels permits a unique delineation of thalamocortical and intracortical components of cortical cell responses based on latency and security of response to peripheral receptor stimulation. When recorded in awake animals or even under very light anesthesia, cortical neurons show two components to their response to whisker movement. Neurons in layer IV of a whisker's primary projection zone respond with short latency (7-10 msec) and a high response magnitude (two or more action potentials (spikes) per stimulus). This "Center Receptive Field" (CRF) for layer IV cells is generated in large part by sensory fiber inputs from the thalamus. The CRF is restricted to 1.4 whiskers on average and is the only response detectable when cortical responses are depressed by deep anesthesia. In the "waking state" the same neuron often will respond to deflection of 4-6 surrounding whiskers, but only at longer latency (15-40 msec) and with fewer spikes per stimulus. These more labile responses form an excitatory surround receptive field (SRF). Sensory information that is transduced by individual whiskers and that generates the SRF of a cortical neuron achieves this added response complexity through intracortical mechanisms. The control of the mechanisms that determine the dissemination of sensory information within cortex include: (1) regulating the level of GABAergic inhibition; and (2) potentiation or depression of the response level generated by repeated sensory experience. State-dependent "modulatory" inputs to cortex, such as the noradrenergic and cholinergic fiber system, could regulate the degree of horizontal spread of a sensory input, in part through global changes in the level of inhibition and/or regulating the amplitude of cortical responses, thereby determining the level of associative interactions between sensory inputs.

Animals↗
PubMed1989

Peripheral nerve damage facilitates functional innervation of brain grafts in adult sensory cortex.

The neural pathways that relay information from cutaneous receptors to the cortex provide the somatic sensory information needed for cortical function. The last sensory relay neurons in this pathway have cell bodies in the thalamus and axons that synapse on neurons in the somatosensory cortex. After cortical lesions that damage mature thalamocortical fibers in the somatosensory cortex, we have attempted to reestablish somatosensory cortical function by grafting embryonic neocortical cells into the lesioned area. Such grafts survive in adult host animals but are not innervated by thalamic neurons, and consequently the grafted neurons show little if any spontaneous activity and no responses to cutaneous stimuli. We have reported that transection of peripheral sensory nerves prior to grafting "conditions" or "primes" the thalamic neurons in the ventrobasal complex so that they extend axons into grafts subsequently placed in the cortical domain of the cut nerve. In this report we present evidence that the ingrowth of ventrobasal fibers leads to graft neurons that become functionally integrated into the sensory circuitry of the host brain. Specifically, the conditioning lesions made prior to grafting produce graft neurons that are spontaneously active and can be driven by natural activation of cutaneous receptors or electrical stimulation of the transected nerve after it regenerates. Furthermore, oxidative metabolism in these grafts reaches levels that are comparable to normal cortex, whereas without prior nerve cut, oxidative metabolism is abnormally low in neocortical grafts. We conclude that damage to the sensory periphery transsynaptically stimulates reorganization of sensory pathways through mechanisms that include axonal elongation and functional synaptogenesis.

Animals↗
PubMed1988

Maintenance of discrete somatosensory maps in subcortical relay nuclei is dependent on an intact sensory cortex.

Lesions of the rat barrelfield cortex drastically alter the discrete representations of the somatosensory periphery in the central nervous system. We have found that lesions placed in the parietal cortex, after the formation of barrels (postnatal day 5), can irreversibly abolish vibrissae- and extremity-related patterns of cytochrome oxidase activity in the principal sensory nucleus of the trigeminal nerve and in the dorsal column nuclei. Furthermore, abnormal patterns of enzymatic activity occur in the remaining primary somatosensory cortex and the ventrobasal nucleus of the thalamus. We conclude that cortical barrels are essential in maintenance of periphery-related discrete morphological organization in the rodent somatosensory system.

Afferent Pathways↗
PubMed1988

Time course of neocortical graft innervation by AChE-positive fibers.

Acetylcholinesterase (AChE)-containing axons are the only extrinsic fibers projecting to the adult cortex that readily innervate embryonic cortical grafts up to normal densities without prior manipulation of the host brain. In the present paper we compare the time course of AChE-positive fiber innervation in the normal mouse cortex with that seen in neocortical grafts by using AChE histochemistry as a marker for presumed cholinergic fibers. Donor tissue was taken at two different stages of gestation; before (embryonic days 12-14, or E12-14) and after (E17-19) the cortical plate is formed. Three features are analyzed: 1) the distribution and density of AChE-containing fibers, 2) the presence of AChE-positive cells, and 3) the distribution of butyrylcholinesterase (BuChE)-positive elements. The modification of Koelle's method used for AChE localization showed AChE-positive fibers in developing parietal neocortex as early as E18-19. The distribution of AChE-labeled fibers in the normal cortex achieves the mature pattern by the end of the third postnatal week. The rate of innervation of transplants takes longer and depends on the age of the donor tissue. Tissue from both donor ages first showed AChE-positive fibers crossing the host-transplant interface by 7 days postsurgery. E17-19 tissue approaches the density of AChE-positive fibers in the normal adult cortex by 15 weeks after grafting, whereas the E12-14 donor tissue does not approach normal innervation densities until after 20 weeks. While the degree of innervation in the E12-14 donor tissue never equalled the surrounding adult cortex within our range of survival times, a few of the E17-19 transplants did develop densities equal to that of the host cortex. AChE-positive cells are first detectable in the normal parietal cortex on the day of birth, peak by the end of the first postnatal week, and then decline in number to the low levels of the mature cortex after the second postnatal week. Grafted cells in E12-14 tissue stain lightly for AChE by 7 days postsurgery, achieve maximal densities by 3 weeks, and become markedly reduced in number and density by 10 weeks. Cells in E17-19 tissue are lightly reactive by 7 days postsurgery, reach maximal numbers by 2 weeks postsurgery, and become similar in number and density to those seen in the mature cortex after 4 weeks. The appearance of BuChE-reactive blood vessels, neurons, and glia in both normal development and in the transplants is described and discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗
PubMed1988

Peripheral nerve transection induces innervation of embryonic neocortical transplants by specific thalamic fibers in adult mice.

Embryonic neocortical tissue survives and differentiates when grafted to injured adult neocortex. While these transplants are readily innervated by the host cholinergic fibers, specific thalamic fibers fail to innervate them. The present study was designed to test whether changing the activity levels of the thalamic ventrobasal projection neurons would promote sprouting of their axons into the embryonic cortical implants placed in the barrel field cortex. To achieve this the main input to these thalamic neurons was eliminated two synapses away, by blocking the peripheral sensory input to the barrel field cortex. Adult hosts underwent unilateral transection of the infraorbital nerve and two days later the contralateral barrel field cortex was lesioned enough to insert an embryonic neocortical graft. Following a one month post-transplantation period we examined the amount of specific thalamic axon ingrowth into the transplants by injecting the ventrobasal nucleus with horseradish peroxidase. The control cases without prior nerve damage confirmed previous observations that ventrobasal nucleus neurons fail to innervate the implanted neocortex. Transection of the infraorbital nerve prior to transplantation resulted in an unprecedented ingrowth of specific thalamic axons into the transplants. There was no significant difference in the amount of thalamic fiber ingrowth into the transplants when the peripheral nerve was (transection) or was not (cautery) allowed to regenerate. However, transection of the infraorbital nerve permits the nerve to regenerate and at least partially reconnect the sensory periphery, thus leading to the possibility of functional integration of the neocortical transplants into the host trigeminal system. The morphology and distribution of host acetylcholinesterase-positive fibers that grow into the transplants under both experimental and control conditions were distinctly different from those of thalamic axons. These results provide the first demonstration of peripheral sensory nerve induction of regenerative propensity in specific thalamocortical projection neurons. The thalamic fiber ingrowth should lead to enhanced functional innervation of the neocortical implants and better incorporation of the graft into the adult host brain circuitry.

Acetylcholinesterase↗
PubMed1988

Basal forebrain lesions facilitate adult host fiber ingrowth into neocortical transplants.

The ability of mature host thalamic neurons to innervate embryonic (E19) cortex when implanted into the cortex of adult hosts was compared in normal and basal forebrain lesioned mice. The ingrowth of mature horseradish peroxidase-labeled thalamic axons into the transplants is facilitated by prior basal forebrain lesions. We discuss the possible reasons for the lesion-induced enhancement of axonal ingrowth, including the possibility that the enhanced ingrowth of thalamic fiber systems may be related to the loss of cortical innervation by extrathalamic brainstem inputs, especially cholinergic afferent fibers. The results support the interpretation that extrathalamic inputs to cortex play a modulatory role in regulating the growth and connections of specific sensory fiber systems during brain responses to injury.

Acetylcholinesterase↗