Evolution of Local Circuit Neurons in Two Sensory Thalamic Nuclei in Amniotes.

Local circuit neurons are present in the thalamus of all vertebrates where they are considered inhibitory. They play an important role in computation and influence the transmission of information from the thalamus to the telencephalon. In mammals, the percentage of local circuit neurons in the dorsal lateral geniculate nucleus remains relatively constant across a variety of species. In contrast, the numbers of local circuit neurons in the ventral division of the medial geniculate body in mammals vary significantly depending on the species examined. To explain these observations, the numbers of local circuit neurons were investigated by reviewing the literature on this subject in these two nuclei in mammals and their respective homologs in sauropsids and by providing additional data on a crocodilian. Local circuit neurons are present in the dorsal geniculate nucleus of sauropsids just as is the case for this nucleus in mammals. However, sauropsids lack local circuits neurons in the auditory thalamic nuclei homologous to the ventral division of the medial geniculate body. A cladistic analysis of these results suggests that differences in the numbers of local circuit neurons in the dorsal lateral geniculate nucleus of amniotes reflect an elaboration of these local circuit neurons as a result of evolution from a common ancestor. In contrast, the numbers of local circuit neurons in the ventral division of the medial geniculate body changed independently in several mammalian lineages.

Thalamic Reticular Nucleus in Caiman crocodilus: Immunohistochemical Staining.

The thalamic reticular nucleus in reptiles, Caiman crocodilus, shares a number of morphological similarities with its counterpart in mammals. In view of the immunohistochemical properties of this nucleus in mammals and the more recently identified complexity of this neuronal aggregate in Caiman, this nucleus was investigated using a number of antibodies. These results were compared with findings described for other amniotes. The following antibodies gave consistent and reproducible results: polyclonal sheep anti-parvalbumin (PV), monoclonal mouse anti-PV, and polyclonal sheep anti-glutamic acid decarboxylase (GAD). In the transverse plane, this nucleus is divided into two. In each part, a compact group of cells sits on top of the fibers of the forebrain bundle with scattered cells among these fibers. In the lateral forebrain bundle, this neuronal aggregate is represented by the dorsal peduncular nucleus and the perireticular nucleus while, in the medial forebrain bundle, these parts are the interstitial nucleus and the scattered cells in this fiber tract. The results of this study are the following. First, the thalamic reticular nucleus of Caiman contains GAD(+) and PV(+) neurons, which is similar to what has been described in other amniotes. Second, the morphology and distribution of many GAD(+) and PV(+) neurons in the dorsal peduncular and perireticular nuclei are similar and suggest that these neurons colocalize these markers. Third, neurons in the interstitial nucleus and in the medial forebrain bundle are GAD(+) and PV(+). At the caudal pole of the thalamic reticular nucleus, PV immunoreactive cells predominated and avoided the central portion of this nucleus where GAD(+) cells were preferentially located. However, GAD(+) cells were sparse when compared with PV(+) cells. This immunohistochemically different area in the caudal pole is considered to be an area separate from the thalamic reticular nucleus.

Development of a statistical model for discrimination of rupture status in posterior communicating artery aneurysms.

BACKGROUND: Intracranial aneurysms at the posterior communicating artery (PCOM) are known to have high rupture rates compared to other locations. We developed and internally validated a statistical model discriminating between ruptured and unruptured PCOM aneurysms based on hemodynamic and geometric parameters, angio-architectures, and patient age with the objective of its future use for aneurysm risk assessment. METHODS: A total of 289 PCOM aneurysms in 272 patients modeled with image-based computational fluid dynamics (CFD) were used to construct statistical models using logistic group lasso regression. These models were evaluated with respect to discrimination power and goodness of fit using tenfold nested cross-validation and a split-sample approach to mimic external validation. RESULTS: The final model retained maximum and minimum wall shear stress (WSS), mean parent artery WSS, maximum and minimum oscillatory shear index, shear concentration index, and aneurysm peak flow velocity, along with aneurysm height and width, bulge location, non-sphericity index, mean Gaussian curvature, angio-architecture type, and patient age. The corresponding area under the curve (AUC) was 0.8359. When omitting data from each of the three largest contributing hospitals in turn, and applying the corresponding model on the left-out data, the AUCs were 0.7507, 0.7081, and 0.5842, respectively. CONCLUSIONS: Statistical models based on a combination of patient age, angio-architecture, hemodynamics, and geometric characteristics can discriminate between ruptured and unruptured PCOM aneurysms with an AUC of 84%. It is important to include data from different hospitals to create models of aneurysm rupture that are valid across hospital populations.

Geometry of saccular cerebral aneurysms not associated with a branch vessel.

OBJECTIVE: Saccular cerebral aneurysms located at nonbranching sites are uncommon. Their distribution, morphological features, and presence of a branch vessel or a tiny perforator(s) separate from the aneurysm neck were investigated. METHODS: From a series of 303 microsurgically clipped saccular cerebral aneurysms, 40 aneurysms were identified at sites not related to a branch vessel. RESULTS: The distribution of aneurysms at nonbranching sites was internal carotid: 21 of 40 (52.5%); main stem of the middle cerebral artery/secondary branch of the middle cerebral artery: 6 of 40 (15%); anterior cerebral artery: 1 of 40 (2.5%); pericallosal artery: 1 of 40 (2.5%); pericallosal/callosal marginal: 3 of 40 (7.5%); vertebral artery: 1 of 40 (2.5%); posterior cerebral artery: 1 of 40 (2.5%); posterior cerebral artery/secondary branch of the posterior cerebral artery: 1 of 40 (2.5%); anterior inferior cerebellar artery: 1 of 40 (2.5%); and distal posterior inferior cerebellar artery: 1 of 40 (2.5%). Branch vessels were seen in 5 cases, and small perforating vessels were observed in 2 instances. CONCLUSIONS: Saccular aneurysms occurring at nonbranching sites are uncommon. Their geometry is particularly favorable for flow directed stents and is most amenable to aneurysms located on large-diameter conducting vessels such as the internal carotid, vertebral, and vertebrobasilar vessels. Smaller parent arteries harboring this type of aneurysm will require new technology to maintain patency of these more distal vessels. If endovascular techniques cannot achieve aneurysm sac obliteration, then open craniotomy and aneurysm clipping will provide a satisfactory alternative.

Nuclei and tracts in the thalamus of crocodiles.

The thalamus is one of the most important divisions of the forebrain because it serves as the major hub for transmission of information between the brainstem and telencephalon. While many studies have investigated the thalamus in mammals, comparable analyses in reptiles are incomplete. To fill this gap in knowledge, the thalamus was investigated in crocodiles using a variety of morphological techniques. The thalamus consists of two parts: a dorsal and a ventral division. The dorsal thalamus was defined by its projections to the telencephalon, whereas the ventral thalamus lacked this circuit. The complement of nuclei in each part of the thalamus was identified and characterized. Alar and basal components of both the dorsal and ventral thalamus were distinguished. Although some alar-derived nuclei in the dorsal thalamus shared certain features, no grouping could account for all of the known nuclei. However, immunohistochemical observations suggested a subdivision of alar-derived ventral thalamic nuclei. In view of this, a different approach to the organization of the dorsal thalamus should be considered. Development of the dorsal thalamus is suggested to be one way to provide a fresh perspective on its organization.

Nuclei and tracts in the epithalamus of crocodiles.

The epithalamus, an area of the dorsal diencephalon found in all vertebrates, consists of the habenula, the subhabenular nuclei, and associated tracts. The habenula is itself divisible into two parts-a medial and a lateral nucleus differing in their inputs, outputs, and cellular morphology. The medial component is related to the limbic system and serotonergic raphe, while the lateral nucleus is more interconnected with the basal ganglia and midbrain dopamine systems. These findings, which come from experiments mainly done on mammals, serve as a basis for comparison with other vertebrates. However, similar studies in other amniotes, such as reptiles, are few. To fill this gap in knowledge, two species of crocodiles were examined utilizing a variety of histological methods in various planes of section. The following results were obtained. First, the habenula was divided into medial and lateral parts based on its cytoarchitecture. Neurons in the medial habenula were small, were closely packed, and had a limited dendritic arbor characterized by unusual distal dendritic appendages, whereas neurons in the lateral habenula were larger, were more loosely packed, and had longer dendritic processes that were commonly beaded. Second, the stria medullaris, the major input to the habenula, was identified by its immunoreactivity to parvalbumin. Third, the fasciculus retroflexus (habenulointerpeduncular tract), the primary output of the habenula, was visualized by staining with acetylcholinesterase. Fourth, nuclei associated with the habenula, the subhabenular nuclei, have been identified and characterized. These features provide a means to recognize the major nuclei and tracts in the epithalamus in crocodiles and are likely applicable to other reptiles.

A different framework to classify preoptic and hypothalamic nuclei in reptiles.

The preoptic area and the hypothalamus are inextricably linked. Together, they represent an area of the forebrain that is essential for survival of the species. Observations in mammals have suggested a classification of these structures into four rostrocaudal areas and three mediolateral zones. Two species of crocodiles were investigated to determine if this scheme or a modification of it could be applied to these reptiles. The resulting classification identified three rostrocaudal areas based on their respective relationship to the ventricular system: preoptic, anterior, and tuberal and four mediolateral zones: ependyma, periventricular, medial, and lateral. This scheme avoided the cumbersome and complicated nomenclature that has traditionally been used for morphologic studies of these areas in other reptiles, including crocodiles. The present classification is simple, straightforward, and readily applicable to other reptiles.

Nuclei and tracts in the pretectum and associated tegmentum of crocodiles.

In all vertebrates, the pretectum and associated tegmentum arise from prosomere 1, but the adult derivatives of these embryonic regions are not well defined in reptiles-especially in crocodiles, the reptilian group most closely related to birds. Despite its importance in vision and visuomotor behavior, descriptions of the pretectum in crocodiles are brief and photographs are lacking. To fill this gap in knowledge, the pretectum and associated tegmentum were examined in two crocodilians, Caiman crocodilus and Alligator mississippiensis, using a variety of histological stains in all three traditional planes of section. These observations were compared with similar studies in other reptiles and birds. These comparisons were hampered by differences in nomenclature and limited data. Nevertheless, pretectal nuclei in receipt of retinal input in crocodiles, other reptiles, and birds were the most easily identified when compared with the present analysis. Despite identifying the traditional nuclei comprising the pretectum of crocodiles, other areas remain to be characterized. Nevertheless, knowledge gained from this description will aid further investigations of this brain region in crocodiles and other reptiles as well as provide a reference for developmental studies in crocodiles.

A rare case of partial skull and brain duplication in a hatchling Alligator mississippiensis.

Errors in development occur in all vertebrates. When severe, these anomalies are lethal and frequently escape attention. In rare cases, animals with profound malformations are born and can provide a glimpse into structures and their respective function that would otherwise go unnoticed. A rare abnormality in a hatchling Alligator mississippiensis is described in which duplication of the skull, face, and brain was incomplete. The rostral skull, face, and associated forebrain, including the olfactory apparatus, were duplicated. However, the caudal skull and brainstem were not. These observations were made with advanced imaging using both computed tomography and magnetic resonance coupled with gross brain dissections. These abnormal features emphasize the complex and intertwined relationship between the development of the brain, face, and skull which are influenced by certain signaling molecules, possible gene mutation(s), and potential environmental factors.

Geometry of saccular, side-branch cerebral aneurysms: implications for treatment.

BACKGROUND: Saccular, side-branch aneurysms are cerebral aneurysms that occur at the junction between a major intracranial artery and a smaller vessel that originates from this parent artery. The geometry of this group of aneurysms was investigated to determine the location of the side branch in relation to the parent vessel or aneurysm neck. METHODS: From a series of microsurgically clipped cerebral aneurysms, 121 side-branch aneurysms had detailed imaging studies and operative records that could be analyzed to determine side-branch vessel origin in relation to the aneurysm neck. RESULTS: The distribution of aneurysms (N) and the number in which the side-branch originated from the parent artery (PA) were: internal carotid ophthalmic (N = 37; PA = 11); internal carotid-superior hypophyseal (N = 2; PA = 2); internal carotid-posterior communicating (N = 28; PA = 11); internal carotid-anterior choroidal (N = 5; PA = 1); main stem of the middle cerebral artery (N = 13; PA = 6); main stem of the anterior cerebral artery (N = 7; PA = 6); secondary branch of the middle cerebral artery (N = 8; PA = 7); secondary branch of the anterior cerebral artery (N = 1; PA = 0); vertebral-posterior inferior cerebellar artery (N = 11; PA = 5); basilar-anterior inferior cerebellar artery (N = 2; PA = 1); and basilar-superior cerebellar artery (N = 7; PA = 5). CONCLUSIONS: Regardless of whether these observations reflect the universe of cerebral aneurysms, a certain percentage of this group of aneurysms will have the side-branch vessel originate from the aneurysm neck. This incidence will likely be influenced by aneurysm location and other factors. Protection of these important vessels from occlusion during endovascular management will require sophisticated endovascular techniques. If these measures are either unavailable or prove unsuccessful, then clipping will be needed if the side-branch vessel originates from the aneurysm neck and its preservation is critical.

Angiographically visible and invisible arteriovenous malformation in the same patient.

A pathologically confirmed angiographically visible and invisible arteriovenous malformation in the same patient is described. The potential clinical significance of these observations is detailed and discussed.

Do crocodiles have a zona incerta?

In mammals, the zona incerta is thought to be involved in a number of behaviors: visceral activity, arousal, attention, and posture and locomotion. These diverse and complex features suggested that the zona incerta functions as a global or integrative node. Nevertheless, despite multiple investigations into its anatomy, physiology, and behavior in a variety of mammals, no specific character identifies the zona incerta besides its appearance in fiber-stained material and its relationship to surrounding structures. One such structure is the thalamic reticular nucleus whose caudal pole often contains some intermingled cells of the zona incerta. In crocodilians, the entopeduncular nucleus (ep) abuts the caudal pole of the thalamic reticular nucleus and displays different immunohistochemical properties and soma size when compared with neurons in the thalamic reticular nucleus itself. To determine if neurons in the ep differed from those in the thalamic reticular nucleus in Alligator mississippiensis, the ep was investigated using Golgi methodology. The morphology and soma size of neurons in the ep differed from those in the thalamic reticular nucleus and indicated that these two areas are indeed separate neuronal aggregates. Based on these data and the known relationships of the zona incerta to surrounding structures in mammals, the ep of crocodilians is suggested to be the counterpart of the zona incerta of mammals.

Cerebral aneurysm classification based on angioarchitecture.

Cerebral aneurysms are commonly named based on their relationship with adjacent vessels in either the anterior or posterior circulation. Although such an approach has long proved useful, this terminology does not take into account potential hemodynamic forces or aneurysm wall properties that are likely to be important for cerebral aneurysm formation, growth, rupture, and treatment. Dissecting, traumatic, false, infectious, and tumorous aneurysms were excluded from review. Only aneurysms in which preoperative imaging studies and operative findings were sufficient for classification were included. All 329 reviewed aneurysms could be divided into 2 groups: fusiform (n=16) and saccular (n=313). Fusiform aneurysms could be subdivided into 2 types: simple (no branch vessel; n=10) and complex (one or more side branches; n=6). Saccular aneurysms could be subdivided into 3 groups: those not associated with a branch vessel (n=31), those associated with a side-branch vessel (n=125), and those located at a bifurcation (n=157). Each of these categories of aneurysms could be classified further based on its association with a conducting, primary, secondary, tertiary, or side-branch vessel. Classification of cerebral aneurysms according to this scheme adequately described all reviewed aneurysms. Grouping aneurysms according to this approach focuses on similarities in angioarchitecture and potential rheologic properties that should prove useful for evaluation of aneurysm growth, rupture, and treatment.

Thalamic reticular nucleus in Alligator mississippiensis: Soma and dendritic morphology.

The thalamic reticular nucleus (TRN) is a critical structure influencing information transfer to the forebrain. In crocodilians, the TRN shares many features with its mammalian counterpart. One area that has not been explored is how individual neurons in the crocodilian TRN compare with those found in mammals. In mammals, TRN neurons are aligned parallel to the external border of the dorsal thalamus, have their dendrites oriented perpendicular to the fibers in the internal capsule, have fine, filamentous dendritic appendages, are either bipolar or multipolar, and are commonly considered to be a homogeneous morphological population of cells. To investigate the cellular morphology of the TRN complex, a Golgi analysis was undertaken in Alligator mississippiensis. This study examined features that have been used in mammals. In Alligator, the four TRN divisions are the dorsal peduncular nucleus, the perireticular nucleus, the interstitial nucleus, and the neurons in the medial forebrain bundle associated with the interstitial nucleus. In crocodilians, the dorsal peduncular nucleus is homologous to the TRN of mammals. From the 1787 drawn neuron profiles in the traditional three planes of section, the following were concluded. First, neurons in each part of the TRN complex in Alligator were similar in morphology. Second, each part of the TRN complex of Alligator contained a heterogenous population of cells. These variations between the cellular morphology of the dorsal peduncular nucleus of crocodilians and the TRN of mammals are speculated to partly result from differences in forebrain organization.

Magnetic resonance diffusion tensor tractography of a midbrain auditory circuit in Alligator.

Knowledge of brain circuitry is critical for understanding the organization, function, and evolution of central nervous systems. Most commonly, brain connections have been elucidated using histological and experimental methods that require animal sacrifice. On the other hand, magnetic resonance diffusion tensor imaging and associated tractography have emerged as a preferred method to noninvasively visualize brain white matter tracts. However, existing studies have primarily examined large, heavily myelinated fiber tracts. Whether tractography can visualize fiber bundles that contain thin and poorly myelinated axons is uncertain. To address this question, the midbrain auditory pathway to the thalamus was investigated in Alligator. This species was chosen because of its evolutionary importance as it is the reptilian group most closely related to birds and because its brain contains many thin and poorly myelinated tracts. Furthermore, this auditory pathway is well documented in other reptiles, including a related crocodilian. Histological observations and experimental determination of anterograde connections confirmed this path in Alligator. Tractography identified these tracts in Alligator and provided a 3-dimensional picture that accurately identified the neural elements of this circuit. In addition, tractography identified one possible unrecognized pathway. These results demonstrate that tractography can visualize circuits containing thin, poorly myelinated fibers. These findings open the door for future studies to examine these types of pathways in other vertebrates.

Spheno-orbital Reconstruction after Meningioma Resection.

This report details a technique for spheno-orbital reconstruction after meningioma resection. The approach uses a life-size skull model generated from a thin-slice craniomaxillofacial computed tomogram. On this skull model, the planned area of bone removal of the involved orbit and sphenoid is outlined on the normal side opposite the lesion. A three-dimensional implant is then generated by reversing the anticipated area of bone resection on the normal side to create a mirror-image implant. This technique resulted in minimal intraoperative implant contouring, decreased surgical time, and satisfactory functional and cosmetic outcome.

Flexible and Lightweight Devices for Wireless Multi-Color Optogenetic Experiments Controllable via Commercial Cell Phones.

Optogenetics provide a potential alternative approach to the treatment of chronic pain, in which complex pathology often hampers efficacy of standard pharmacological approaches. Technological advancements in the development of thin, wireless, and mechanically flexible optoelectronic implants offer new routes to control the activity of subsets of neurons and nerve fibers in vivo. This study reports a novel and advanced design of battery-free, flexible, and lightweight devices equipped with one or two miniaturized LEDs, which can be individually controlled in real time. Two proof-of-concept experiments in mice demonstrate the feasibility of these devices. First, we show that blue-light devices implanted on top of the lumbar spinal cord can excite channelrhodopsin expressing nociceptors to induce place aversion. Second, we show that nocifensive withdrawal responses can be suppressed by green-light optogenetic (Archaerhodopsin-mediated) inhibition of action potential propagation along the sciatic nerve. One salient feature of these devices is that they can be operated via modern tablets and smartphones without bulky and complex lab instrumentation. In addition to the optical stimulation, the design enables the simultaneously wireless recording of the temperature in proximity of the stimulation area. As such, these devices are primed for translation to human patients with implications in the treatment of neurological and psychiatric conditions far beyond chronic pain syndromes.

Cell proliferation during early diencephalon development in Alligator.

Using immunocytochemical methodology, cell proliferation was investigated in Alligator during early diencephalon development. These results were compared with cell proliferation during early hindbrain formation in this same species using identical techniques. The pattern of cell proliferation in the diencephalon differed from that observed in the rhombencephalon. If cell proliferation is a factor influencing brain development, then the diencephalon of Alligator may be built differently from the hindbrain.

Early diencephalon development in Alligator.

Diencephalon development was investigated in a reptilian embryo, Alligator mississipiensis, beginning at a single compartment stage and continuing until internal subdivisions were present within major units. A variety of morphological techniques were used: immunocytochemistry, histochemistry, and cresyl violet staining. The diencephalon begins as a single unit. In the transverse domain, the diencephalon subsequently divides into two: the parencephalon and the synencephalon. The parencephalon then splits into the parencephalon anterior and parencephalon posterior. Still later, the synencephalon undergoes parcellation into the synencephalon anterior and synencephalon posterior. Subsequently, internal subdivisions occur in each of these four compartments. When the diencephalon has become subdivided into two compartments and continuing until internal subdivisions are present in each unit, a longitudinal border separating a dorsal, presumed alar plate, from a ventral, presumed basal plate, was seen. No clear cut subunits were reliably identified in the telencephalon or secondary prosencephalon during this period of early development in Alligator. Early diencephalon development in birds (chick) and mammals (humans) follows a similar pattern. Specifically, a single diencephalic compartment divides into two zones: the parencephalon and synencephalon. Subsequently, the parencephalon becomes subdivided into an anterior and posterior unit. Some studies, including the present one, have noted further parcellation of the synencephalon into an anterior and posterior component, whereas others have not. Notwithstanding differences as to whether the synencephalon is a single unit or not, these detailed analyses in reptiles (Alligator), birds (chick), and mammals (humans), suggest that the initial pattern of early diencephalon development in amniotes is similar.

Thrombosis, growth, recanalization, and rupture of a saccular, non-giant cerebral aneurysm.

A partly thrombosed, saccular, non-giant left internal carotid artery aneurysm was discovered during an evaluation for headaches in a 75-year-old woman. A mirror-image aneurysm of the right internal carotid artery was also found. During the course of about a year, the left-sided aneurysm thrombosed, grew to giant proportions, recanalized, and ruptured. During this same time, the right-sided aneurysm remained unchanged in size or shape. Even a saccular, non-giant, thrombosed aneurysm can be potentially dangerous. Such an aneurysm requires careful monitoring. If clinically appropriate, aneurysm treatment is indicated.