Connectivity In Rats Research Articles

Investigating cortical complexity and connectivity in rats with schizophrenia.

The above studies indicate that the SCZ animal model has abnormal gamma oscillations and abnormal functional coupling ability of brain regions at the cortical level. However, few researchers have focused on the correlation between brain complexity and connectivity at the cortical level. In order to provide a more accurate representation of brain activity, we studied the complexity of electrocorticogram (ECoG) signals and the information interaction between brain regions in schizophrenic rats, and explored the correlation between brain complexity and connectivity. We collected ECoG signal from SCZ rats. The frequency domain and time domain functional connectivity of SCZ rats were evaluated by magnitude square coherence and mutual information (MI). Permutation entropy (PE) and permutation Lempel-Ziv complexity (PLZC) were used to analyze the complexity of ECoG, and the relationship between them was evaluated. In addition, in order to further understand the causal structure of directional information flow among brain regions, we used phase transfer entropy (PTE) to analyze the effective connectivity of the brain. Firstly, in the high gamma band, the complexity of brain regions in SCZ rats is higher than that in normal rats, and the neuronal activity is irregularity. Secondly, the information integration ability of SCZ rats decreased and the communication of brain network information was hindered at the cortical level. Finally, compared with normal rats, the causal relationship between brain regions of SCZ rats was closer, but the information interaction center was not clear. The above findings suggest that at the cortical level, complexity and connectivity are valid biomarkers for identifying SCZ. This bridges the gap between peak potentials and EEG. This may help to understand the pathophysiological mechanisms at the cortical level in schizophrenics.

Factors influencing JUUL e-cigarette nicotine vapour-induced reward, withdrawal, pharmacokinetics and brain connectivity in rats: sex matters

Though vaping likely represents a safer alternative to smoking, it is not without risks, many of which are not well understood, especially for vulnerable populations. Here we evaluate the sex- and age-dependent effects of JUUL nicotine vapour in rats. Following passive nicotine vapour exposures (from 59 mg/ml JUUL nicotine pods), rats were evaluated for reward-like behaviour, locomotion, and precipitated withdrawal. Pharmacokinetics of nicotine and its metabolites in brain and plasma and the long-term impact of nicotine vapour exposure on functional magnetic resonance imaging-based brain connectivity were assessed. Adult female rats acquired conditioned place preference (CPP) at a high dose (600 s of exposure) of nicotine vapour while female adolescents, as well as male adults and adolescents did not. Adult and adolescent male rats displayed nicotine vapour-induced precipitated withdrawal and hyperlocomotion, while both adult and adolescent female rats did not. Adult females showed higher venous and arterial plasma and brain nicotine and nicotine metabolite concentrations compared to adult males and adolescent females. Adolescent females showed higher brain nicotine concentration compared to adolescent males. Both network-based statistics and between-component group connectivity analyses uncovered reduced connectivity in nicotine-exposed rats, with a significant group by sex interaction observed in both analyses. The short- and long-term effects of nicotine vapour are affected by sex and age, with distinct behavioural, pharmacokinetic, and altered network connectivity outcomes dependent on these variables.

Single subanesthetic dose of ketamine produces delayed impact on brain [18F]FDG PET imaging and metabolic connectivity in rats.

Ketamine, a glutamate NMDA receptor antagonist, is suggested to act very rapidly and durably on the depressive symptoms including treatment-resistant patients but its mechanisms of action remain unclear. There is a requirement for non-invasive biomarkers, such as imaging techniques, which hold promise in monitoring and elucidating its therapeutic impact. We explored the glucose metabolism with [18F]FDG positron emission tomography (PET) in ten male rats in a longitudinal study designed to compare imaging patterns immediately after acute subanaesthetic ketamine injection (i.p. 10 mg/kg) with its sustained effects, 5 days later. Changes in [18F]FDG uptake following ketamine administration were estimated using a voxel-based analysis with SPM12 software, and a region of interest (ROI) analysis. A metabolic connectivity analysis was also conducted to estimate the immediate and delayed effects of ketamine on the inter-individual metabolic covariance between the ROIs. No significant difference was observed in brain glucose metabolism immediately following acute subanaesthetic ketamine injection. However, a significant decrease of glucose uptake appeared 5 days later, reflecting a sustained and delayed effect of ketamine in the frontal and the cingulate cortex. An increase in the raphe, caudate and cerebellum was also measured. Moreover, metabolic connectivity analyses revealed a significant decrease between the hippocampus and the thalamus at day 5 compared to the baseline. This study showed that the differences in metabolic profiles appeared belatedly, 5 days after ketamine administration, particularly in the cortical regions. Finally, this methodology will help to characterize the effects of future molecules for the treatment of treatment resistant depression.

Early Life Pain Experience Changes Adult Functional Pain Connectivity in the Rat Somatosensory and the Medial Prefrontal Cortex.

Early life pain (ELP) experience alters adult pain behavior and increases injury-induced pain hypersensitivity, but the effect of ELP on adult functional brain connectivity is not known. We have performed continuous local field potential (LFP) recording in the awake adult male rats to test the effect of ELP on functional cortical connectivity related to pain behavior. Primary somatosensory cortex (S1) and medial prefrontal cortex (mPFC) LFPs evoked by mechanical hindpaw stimulation were recorded simultaneously with pain reflex behavior for 10 d after adult incision injury. We show that, after adult injury, sensory evoked S1 LFP δ and γ energy and S1 LFP δ/γ frequency coupling are significantly increased in ELP rats compared with controls. Adult injury also induces increases in S1-mPFC functional connectivity, but this is significantly prolonged in ELP rats, lasting 4 d compared with 1 d in controls. Importantly, the increases in LFP energy and connectivity in ELP rats were directly correlated with increased behavioral pain hypersensitivity. Thus, ELP alters adult brain functional connectivity, both within and between cortical areas involved in sensory and affective dimensions of pain. The results reveal altered brain connectivity as a mechanism underlying the effects of ELP on adult pain perception.SIGNIFICANCE STATEMENT Pain and stress in early life has a lasting impact on pain behavior and may increase vulnerability to chronic pain in adults. Here, we record pain-related cortical activity and simultaneous pain behavior in awake adult male rats previously exposed to pain in early life. We show that functional connectivity within and between the somatosensory cortex and the medial prefrontal cortex (mPFC) is increased in these rats and that these increases are correlated with their behavioral pain hypersensitivity. The results reveal that early life pain (ELP) alters adult brain connectivity, which may explain the impact of childhood pain on adult chronic pain vulnerability.

Examining ventral subiculum and basolateral amygdala projections to the nucleus accumbens shell: Differential expression of VGLuT1, VGLuT2 and VGaT in the rat

Projections to the striatum are well-identified. For example, in the ventral striatum, two major inputs to the medial nucleus accumbens shell include the ventral subiculum and basolateral amygdala. However, the chemical phenotype(s) of these projection neurons remain unclear. In this study, we examined amygdalostriatal and corticostriatal connectivity in rats using injections of the retrograde tracer cholera toxin b into the nucleus accumbens shell. To determine the neurotransmitter identity of projection neurons, we combined retrograde tracing with RNAscope in-situ hybridization, using mRNA probes against vesicular transporters associated with glutamatergic (VGluT1 – Slc17a7, VGluT2 – Slc17a6) or GABAergic (VGaT – Slc32a1) neurotransmission. Confocal imaging was used to examine vesicular transporter mRNA expression in the ventral subiculum and basolateral amygdala inputs to the nucleus accumbens shell. Both projections contained mostly VGluT1-expressing neurons. Interestingly, almost a quarter of ventral subiculum to nucleus accumbens shell projections co-expressed VGluT1 and VGluT2 compared to a relatively small number (∼3%) that were co-expressed in basolateral amygdala to nucleus accumbens shell afferents. However, almost a quarter of basolateral amygdala to nucleus accumbens shell projections were VGaT-positive. These findings highlight the diverse proportions of glutamatergic and GABAergic afferents in two major projections to the nucleus accumbens shell and raise important questions for functional studies.

A study of adeno-associated virus in cortical-thalamostriatal pathway

The cortical-thalamostriatal pathway constitutes the cortico-basal ganglia circuit and plays a critical role in the control of movement. Emerging evidence shows that center median/parafascicular (CM/Pf) neurons are lost in Parkinson's disease (PD) patients with motor deficits and CM/Pf neurons send massive and topographically organized projections to specific regions of the dorsal striatum, but provide only minor inputs to the cerebral cortex. However, anatomical connectivity in the cortical-thalamostriatal pathway are poorly understood at present. In the present study, we used a neural tracing method with adeno-associated virus (AAV) to monitor the cortical-thalamostriatal connectivity in rats. We found that parafascicular nucleus (PF) not only project directly to the striatum but send minor inputs to the cortical regions. It was manifested by green fluorescent protein (GFP) expressing fibers observed in dorsolateral striatum (DLS) and the primary motor cortex (M1) after adeno-associated virus serotype 2/9 (AAV2/9)-GFP injection into PF and GFP expressing cells observed in PF after injection AAV2/retro-GFP into M1. And the PF also receive projections from the DLS and it was demonstrated by GFP expressing fibers in PF after AAV2/9-GFP injection into DLS and GFP expressing cells in DLS after injection AAV2/retro-GFP into PF. Histological and behavioral analysis revealed that AAV vector transduction cause damage in neurons on the injection sites and also damage motor activity of rats suggesting caution in clinical application.

Isoflurane affects brain functional connectivity in rats 1 month after exposure

Isoflurane, the most commonly used preclinical anesthetic, induces brain plasticity and long-term cellular and molecular changes leading to behavioral and/or cognitive consequences. These changes are most likely associated with network-level changes in brain function. To elucidate the mechanisms underlying long-term effects of isoflurane, we investigated the influence of a single isoflurane exposure on functional connectivity, brain electrical activity, and gene expression.Male Wistar rats (n = 22) were exposed to 1.8% isoflurane for 3 h. Control rats (n = 22) spent 3 h in the same room without exposure to anesthesia. After 1 month, functional connectivity was evaluated with resting-state functional magnetic resonance imaging (fMRI; n = 6 + 6) and local field potential measurements (n = 6 + 6) in anesthetized animals. A whole genome expression analysis (n = 10+10) was also conducted with mRNA-sequencing from cortical and hippocampal tissue samples.Isoflurane treatment strengthened thalamo-cortical and hippocampal-cortical functional connectivity. Cortical low-frequency fMRI power was also significantly increased in response to the isoflurane treatment. The local field potential results indicating strengthened hippocampal-cortical alpha and beta coherence were in good agreement with the fMRI findings. Furthermore, altered expression was found in 20 cortical genes, several of which are involved in neuronal signal transmission, but no gene expression changes were noted in the hippocampus.Isoflurane induced prolonged changes in thalamo-cortical and hippocampal-cortical function and expression of genes contributing to signal transmission in the cortex. Further studies are required to investigate whether these changes are associated with the postoperative behavioral and cognitive symptoms commonly observed in patients and animals.

Rat Locomotion Detection Based on Brain Functional Directed Connectivity from Implanted Electroencephalography Signals.

Previous findings have suggested that the cortex involved in walking control in freely locomotion rats. Moreover, the spectral characteristics of cortical activity showed significant differences in different walking conditions. However, whether brain connectivity presents a significant difference during rats walking under different behavior conditions has yet to be verified. Similarly, whether brain connectivity can be used in locomotion detection remains unknown. To address those concerns, we recorded locomotion and implanted electroencephalography signals in freely moving rats performing two kinds of task conditions (upslope and downslope walking). The Granger causality method was used to determine brain functional directed connectivity in rats during these processes. Machine learning algorithms were then used to categorize the two walking states, based on functional directed connectivity. We found significant differences in brain functional directed connectivity varied between upslope and downslope walking. Moreover, locomotion detection based on brain connectivity achieved the highest accuracy (91.45%), sensitivity (90.93%), specificity (91.3%), and F1-score (91.43%). Specifically, the classification results indicated that connectivity features in the high gamma band contained the most discriminative information with respect to locomotion detection in rats, with the support vector machine classifier exhibiting the most efficient performance. Our study not only suggests that brain functional directed connectivity in rats showed significant differences in various behavioral contexts but also proposed a method for classifying the locomotion states of rat walking, based on brain functional directed connectivity. These findings elucidate the characteristics of neural information interaction between various cortical areas in freely walking rats.

Electroacupuncture promotes motor function and functional connectivity in rats with ischemic stroke: an animal resting-state functional magnetic resonance imaging study.

To evaluate whether electroacupuncture (EA) treatment at LI11 and ST36 could reduce motor impairments and enhance brain functional recovery in a rat model of ischemic stroke. A rat model of middle cerebral artery occlusion (MCAO) was established. EA at LI11 and ST36 was started at 24 h (MCAO + EA group) after ischemic stroke modeling. Untreated model (MCAO) and sham-operated (Sham) groups were included as controls. The neurological deficits of all groups were assessed using modified neurologic severity scores (mNSS) at 24 h and 14 days after MCAO. To further investigate the effect of EA on infarct volume and brain function, functional magnetic resonance imaging was used to estimate the size of the brain lesions and neural activities of each group at 14 days after ischemic stroke. EA treatment of MCAO rats led to a significant reduction in the infarct volumes accompanied by functional recovery, reflected in improved mNSS outcomes and motor functional performances. Furthermore, functional connectivity between the left motor cortex and left cerebellum posterior lobe, right motor cortex, left striatum and bilateral sensory cortex were decreased in MCAO group but increased after EA treatment. EA at LI11 and ST36 could enhance the functional connectivity between the left motor cortex and the motor function-related brain regions, including the motor cortex, sensory cortex and striatum, in rats. EA exhibits potential as a treatment for ischemic stroke.

Aberrant insular cortex connectivity in abstinent alcohol-dependent rats is reversed by dopamine D3 receptor blockade.

A few studies have reported aberrant functional connectivity in alcoholic patients, but the specific neural circuits involved remain unknown. Moreover, it is unclear whether these alterations can be reversed upon treatment. Here, we used functional MRI to study resting state connectivity in rats following chronic intermittent exposure to ethanol. Further, we evaluated the effects of SB‐277011‐a, a selective dopamine D3 receptor antagonist, known to decrease ethanol consumption. Alcohol‐dependent and control rats (N = 13/14 per group), 3 weeks into abstinence, were administered SB‐277011‐a or vehicle before fMRI sessions. Resting state connectivity networks were extracted by independent component analysis. A dual‐regression analysis was performed using independent component maps as spatial regressors, and the effects of alcohol history and treatment on connectivity were assessed. A history of alcohol dependence caused widespread reduction of the internal coherence of components. Weaker correlation was also found between the insula cortex (IC) and cingulate cortices, key constituents of the salience network. Similarly, reduced connectivity was observed between a component comprising the anterior insular cortex, together with the caudate putamen (CPu‐AntIns), and the posterior part of the IC. On the other hand, postdependent rats showed strengthened connectivity between salience and reward networks. In particular, higher connectivity was observed between insula and nucleus accumbens, between the ventral tegmental area and the cingulate cortex and between the VTA and CPu‐AntIns. Interestingly, aberrant connectivity in postdependent rats was partially restored by acute administration of SB‐277011‐a, which, conversely, had no significant effects in naïve rats.

Abnormal Metabolic Connectivity in Rats at the Acute Stage of Ischemic Stroke.

Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion (MCAO) at the acute stage using 18F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemisphere, and increased metabolism mainly in the contralesional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic connectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.

Cortical high gamma network oscillations and connectivity: a translational index for antipsychotics to normalize aberrant neurophysiological activity

Oscillatory activity in the gamma frequency range is a critical mechanism, which integrates neural networks within and across brain structures during cognitive processes. In schizophrenia, abnormalities in high gamma oscillations are ubiquitous and most likely reflect dysfunction in neuronal networks. In conscious rats, disturbed network oscillations associated with positive symptoms and cognitive deficits were modeled in different cortical areas by the dopaminergic agonist (amphetamine) and the N-methyl-D-aspartate (NMDA) receptor antagonists (PCP and MK801). Subsequently, the efficacies of marketed atypical antipsychotics (olanzapine, risperidone, and clozapine) to normalize dysfunctional oscillations and network connectivity were examined. Acute NMDA antagonists elicited aberrant synchrony in the gamma frequency oscillations. In addition, coherent slow alpha network activity was observed with MK801 and amphetamine, both of whose oscillatory rhythms were correlated with pronounced locomotor activity. All antipsychotics commonly decreased slow alpha and high gamma network oscillations in different cortical regions as well as motion behavior. In the combined treatments, antipsychotics attenuated NMDA antagonist-induced abnormalities in functional network oscillations and connectivity, whose effects on motor behavior is mechanistically related. These results suggest that pharmacologically induced disruption of cortical gamma oscillations and network connectivity in rats is a candidate model to study dysfunctional oscillatory patterns described in positive and negative symptoms of schizophrenia. The efficacy of antipsychotics to rescue cortical network oscillatory patterns is in line with the idea that glutamatergic and dopaminergic systems play a role in maintaining the integrity of cortical circuits. Thus, gamma oscillations could provide a powerful translational index to assess the integrity of neural networks and to evaluate the efficacy of drugs with potential antipsychotic properties.

The fear circuit of the mouse forebrain: connections between the mediodorsal thalamus, frontal cortices and basolateral amygdala.

A large forebrain circuit, including the thalamus, amygdala and frontal cortical regions, is responsible for the establishment and extinction of fear-related memories. Understanding interactions among these three regions is critical to deciphering the basic mechanisms of fear. With the advancement of molecular and optogenetics techniques, the mouse has become the main species used to study fear-related behaviours. However, the basic connectivity pattern of the forebrain circuits involved in processing fear has not been described in this species. In this study we mapped the connectivity between three key nodes of the circuit, i.e. the basolateral nucleus of the amygdala (BLA), the mediodorsal nucleus of the thalamus (MD) and the medial prefrontal cortex, which were shown to have closed triangular connectivity in rats. In contrast to rat, we found no evidence for this closed loop in mouse. There was no major input from the BLA to the MD and little overlap between medial prefrontal regions connected with both the BLA and MD. The common nodes in the frontal cortex, which displayed reciprocal connection with both the BLA and MD were the agranular insular cortex and the border zone of the cingulate and secondary motor cortex. In addition, the BLA can indirectly affect the MD via the orbital cortex. We attribute the difference between our results and earlier rat studies to methodological problems rather than to genuine species difference. Our data demonstrate that the BLA and MD communicate via cortical sectors, the roles in fear-related behaviour of which have not been extensively studied. In general, our study provides the morphological framework for studies of murine fear-related behaviours.

P4‐257: Changes in fMRI resting state functional connectivity in rats after acute and repeat dosing with Pioglitazone

P4‐257: Changes in fMRI resting state functional connectivity in rats after acute and repeat dosing with Pioglitazone

Altered Thalamocortical Functional Connectivity by Propofol Anesthesia in Rats

Anesthesia, a state of profound central nervous system suppression, involves a sequence of events that is still not well understood. In the present study, we examined the action of propofol (a sedative-hypnotic drug commonly used as anesthetic) on thalamocortical functional connectivity in rats by using functional connectivity magnetic resonance imaging (fcMRI) with a 3.0-tesla MR scanner. Intraperitoneal injections of propofol (80 or 160 mg/kg) were administered to Sprague-Dawley rats. Synchronized low-frequency fluctuations (LFF) of blood oxygen level-dependent (BOLD) signals were found between the thalamic and somatosensory cortices (S1/S2) after administration of 80 mg/kg propofol. However, after application of 160 mg/kg propofol, synchronized LFF of BOLD signals disappeared. These observations indicate that thalamocortical connectivity may play an important role in propofol anesthesia. We also observed that regionally specific long-range correlations of spontaneous low-frequency physiological fluctuations in BOLD signals may be present across somatosensory networks of the brain in the absence of external stimulation. However, our experiment suggests that fcMRI can be used to investigate brain networks that exhibit correlated fluctuations.

Changes in efferent and afferent connectivity in rats with induced cerebrocortical microgyria

Changes in efferent and afferent connectivity in rats with induced cerebrocortical microgyria

Changes in efferent and afferent connectivity in rats with induced cerebrocortical microgyria

Freezing injury to the cortical plate at postnatal day (P) 1 initiates a cascade of events that ultimately result in a focal neocortical malformation resembling human 4-layered microgyria. This malformation has been associated with widespread changes in neocortical and thalamic architecture and physiology. It was hypothesized that at least some of these alterations could result from connectional reorganization following early injury. The current experiment was designed to delineate the efferent and afferent connections between the cerebral hemispheres and between the cortex and thalamus of rats with induced cerebrocortical microgyria. Microgyria were induced in the parietal cortex of rats by freezing injury on postnatal day 1. In adulthood, injections of biotinylated dextran amine were made either in the microgyric cortex, in homologous regions of the opposite hemisphere, or in ipsilateral ventrobasal complex of the thalamus. Appropriately directed connections to homotopic areas were seen in some but not all microgyric rats. In addition, heterotopic projections to frontal and secondary sensorimotor cortices were noted. Projections from homotopic regions in the hemisphere opposite to the malformation terminated most often in the medial portions of the microgyrus or avoided it entirely. There were almost no thalamocortical or corticothalamic projections between the ventrobasal complex and the microgyrus itself, although a dense plexus of thalamocortical fibers was often noted at the border between the malformed and normal cortex. These connectional changes may help explain disturbances in architecture, physiology, and behavior associated with these focal malformations.

Intermittent treatment with human parathyroid hormone (hPTH[1-34]) increased trabecular bone volume but not connectivity in osteopenic rats.

Previous studies have determined that intermittent parathyroid hormone (PTH) therapy increases bone mass and improves biomechanical strength in osteopenic animal models. The purpose of this investigation was to determine if intermittent human parathyroid hormone (hPTH[1-34]) therapy increased trabecular bone volume and connectivity in a rat model of established osteopenia using three-dimensional (3D) ex vivo in situ morphometry by X-ray tomographic methods (XTM). Six-month-old retired Sprague-Dawley breeder rats were used. Thirty animals were ovariectomized (OVX) and six were Sham operated. On day 56, post-OVX, a prePTH-treatment OVX groups was sacrificed. The remaining OVX animals were randomized into four groups of six animals each, given injections 5 out of every 7 days for 28 days of either vehicle or hPTH(1-34) at 4, 40, or 400 microg/kg of body weight (BW)/day and were sacrificed on day 84 post-OVX. At sacrifice, the left proximal tibias were harvested for XTM scans. hPTH(1-34) at medium and high doses significantly increased trabecular bone volume and trabecular thickness compared with ovariectomized animals treated with vehicle (p<0.05). The trabecular bone volume was equal to or greater than the Sham-operated animals in both hPTH(1-34) 40 and 400 microg/kg of BW treatment groups. Trabecular bone connectivity decreased by nearly 50% compared to the S ham-operated group at day 84 post-OVX and did not increase with any of the hPTH(1-34) treatments. Intermittent hPTH(1-34) treatment is osteopenic OVX rats increased trabecular bone volume to control levels or higher by thickening existing trabeculae. Human PTH(1-34) did not re-establish connectivity when therapy was started after 50% of the trabecular connectivity was lost. We hypothesize that to re-establish trabecular connectivity, a therapeutic intervention would have to be given before a significant distance between trabeculae has developed. Further studies will need to be done to refute or confirm our hypothesis.

Fetal brain grafts induce recovery of learning deficits and connectivity in rats with gustatory neocortex lesion

Three groups of rats showing disrupted taste aversion due to gustatory neocortex lesions, were studied. One group received a transplant of homotopic cortical tissue, another of heterotopic tectal tissue, obtained from 17-day-old fetuses. The third group remained without transplant as a lesioned control group. Comparisons of the taste aversion scores before and after graft, revealed that cortical grafted animals significantly improved the taste aversion, whereas those which received tectal grafts, and the cortical-lesioned controls did not. Moreover, results with horseradish peroxidase (HRP) histochemistry revealed that the homotopic, but not the heterotopic, brain transplants were able to re-establish connections with amygdala and with the ventromedial nucleus of the thalamus areas who normally kept connectivity with the gustatory neocortex. These results support the hypothesis that fetal brain transplants can re-establish cognitive functions, as well as connectivity with its host tissue.