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A Pitkänen

Publications and source records attributed to A Pitkänen.

At least 19 recordsLinked to original sources
PubMed1998

Intrinsic connections of the rat amygdaloid complex: projections originating in the central nucleus.

Inputs from the amygdaloid and extraamygdaloid areas terminate in various divisions of the central nucleus. To elucidate the interconnections between the different regions of the central nucleus and its connectivity with the other amygdaloid areas, we injected the anterograde tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L) into the capsular, lateral, intermediate, and medial divisions of the central nucleus in rat. There were a number of labeled terminals near the injection site within each division. The intrinsic connections between the various divisions of the central nucleus were organized topographically and originated primarily in the lateral division, which projected to the capsular and medial divisions. Most of the connections were unidirectional, except in the capsular division, which received a light reciprocal projection from its efferent target, the medial division. The intermediate division did not project to any of the other divisions of the central nucleus. Extrinsic projections from the central nucleus to the other amygdaloid nuclei were meager. Light projections were observed in the parvicellular division of the basal nucleus, the anterior cortical nucleus, the amygdalohippocampal area, and the anterior amygdaloid area. No projections to the contralateral amygdala were found. These data show that the central nucleus has a dense network of topographically organized intradivisional and interdivisional connections that may integrate the intraamygdaloid and extraamygdaloid information entering the different regions of the central nucleus. The sparse reciprocal connections to the other amygdaloid nuclei suggest that the central nucleus does not regulate the other amygdaloid regions but, rather, executes the responses evoked by the other amygdaloid nuclei that innervate the central nucleus.

Amygdala↗
PubMed1998

Calretinin-immunoreactive terminals make synapses on calbindin D28k-immunoreactive neurons in the lateral nucleus of the human amygdala.

A double-labeling immunohistochemical procedure and correlated light and electron microscopy were used to examine if calretinin-immunoreactive terminals make synapses on calbindin D28k-positive cells. In the lateral nucleus of the human amygdala, calretinin terminals make symmetric-like synapses on the somata and proximal dendrites of calbindin D28k-labeled cells. Our data provide the first evidence that neurons which contain two different calcium-binding proteins form synaptic contacts with each other in the human amygdala.

Adult↗
PubMed1998

Recurrent seizures may cause hippocampal damage in temporal lobe epilepsy.

OBJECTIVE: To investigate whether recurrent seizures cause hippocampal damage in temporal lobe epilepsy (TLE). PATIENTS: Eighteen patients with newly diagnosed cryptogenic TLE, 14 patients with chronic well-controlled cryptogenic TLE, 32 patients with chronic drug-resistant cryptogenic TLE, and 25 healthy subjects were studied. MEASUREMENTS: Hippocampal MRI volumetry and T2 relaxometry were used. RESULTS: Chronic drug-resistant patients with seizure focus in the left temporal lobe had an 18% smaller left hippocampus and chronic drug-resistant patients with seizure focus in the right temporal lobe had a 14% smaller right hippocampus than did the control group (p < 0.05). Chronic drug-resistant patients with seizure focus on the left side had longer T2 relaxation times in the body of the left hippocampus than did the control group (p < 0.001) and chronic drug-resistant patients with seizure focus on the right side had longer T2 relaxation times in the body of the right hippocampus than did the control subjects (p < 0.01). In all patients with a left seizure focus, the left hippocampal volume correlated inversely with the estimated total number of partial (r = -0.391, p < 0.01) or generalized (r = -0.312, p < 0.05) seizures the patient had experienced. The prolongation of the left T2 relaxation time in the body of the hippocampus correlated with the total number of both partial (r = 0.670, p < 0.001) and generalized (r = 0.481, p < 0.001) seizures and with the duration of TLE symptoms (r = 0.580, p < 0.001). CONCLUSIONS: In patients with cryptogenic epilepsy, recurrent seizures may cause damage to the hippocampus throughout the lifetime of the patient.

Adolescent↗
PubMed1998

MR volumetric analysis of the human entorhinal, perirhinal, and temporopolar cortices.

PURPOSE: Our purpose was to investigate the normal volumes of the human entorhinal, perirhinal, and temporopolar cortices on MR imaging studies using a customized program. METHODS: We designed a protocol in which the volumes of the entorhinal, perirhinal, and temporopolar cortices were determined from coronal MR images using anatomic landmarks defined on the basis of cytoarchitectonic analyses of 49 autopsy cases. MR volumetry of these cortical areas was performed in 52 healthy volunteers. RESULTS: The overall mean volumes were 1768 +/- 328 mm3/1558 +/- 341 mm3 (right/left) for the entorhinal cortex, 2512 +/- 672 mm3/2572 +/- 666 mm3 for the perirhinal cortex, and 2960 +/- 623 mm3/3091 +/- 636 mm3 for the temporopolar cortex. The right entorhinal cortex was 12% larger than the left. The volume of the temporopolar cortex was reduced bilaterally by 13% in the older age group compared with younger subjects, while the volumes of the entorhinal and perirhinal cortices were unaffected by age. There were no differences between men and women in the volumes of any of the three cortices. CONCLUSION: Our method provides a tool by which to measure volumes of the entorhinal, perirhinal, and temporopolar cortices on coronal MR images.

Adolescent↗
PubMed1997

Distribution of parvalbumin-, calretinin-, and calbindin-D28k-immunoreactive neurons and fibers in the human entorhinal cortex.

Parvalbumin, calretinin, and calbindin-D28k are calcium-binding proteins that are located in largely nonoverlapping neuronal populations in the brain. The authors studied the distribution of parvalbumin-, calretinin-, and calbindin-D28k-immunoreactive (ir) cells, fibers, terminals, and neuropil in the eight subfields of the human entorhinal cortex. The distribution of each of the three calcium-binding proteins largely followed the cytoarchitectonic borders of the eight entorhinal subfields, although the regional and laminar distributions of the three proteins were segregated rather than overlapping. The highest density of parvalbumin-ir neurons and terminals was found in the caudal and lateral subfields of the entorhinal cortex. Calretinin and calbindin-D28k immunoreactivities were high rostromedially, although a large number of calretinin and calbindin-D28k neurons were also found in the caudal subfields. All parvalbumin-ir cells had a morphological appearance of nonpyramidal neurons. Parvalbumin-ir terminals formed basket-like formations around unstained somata and cartridges, suggesting that parvalbumin neurons compose a subpopulation of gamma-aminobutyric acid (GABA)ergic basket cells and chandelier cells, respectively. Although calretinin and calbindin-D28k were also found in numerous nonpyramidal neurons, both were also located in pyramidal-shaped neurons in layers V and VI (calretinin) and in layers II and III (calbindin) of the entorhinal cortex, suggesting that they play roles in projection neurons as well. Moreover, the high density of nonpyramidal neurons containing calcium-binding proteins in layers II and III of the entorhinal cortex suggests that they form an integral component of a network that controls the entorhinal outputs to the hippocampus. Furthermore, the largely nonoverlapping distributions of the parvalbumin-, calretinin-, and calbindin-ir neuronal populations in the entorhinal cortex indicate that each of them may modulate a different subset of topographically organized entorhinal outputs.

Adult↗
PubMed1997

Distribution of calretinin-immunoreactivity in the rat entorhinal cortex: coexistence with GABA.

Inhibitory neurons in the entorhinal cortex control information flow between the cortical areas and the hippocampus. We characterized the inhibitory circuits in the rat entorhinal cortex by analyzing the distribution of calretinin-immunoreactivity and its colocalization with glutamate decarboxylase (GAD) and gamma-aminobutyric acid (GABA). The location of calretinin-immunoreactive (IR) neurons and terminals varies between the different layers and subfields of the entorhinal cortex. The immunopositive neurons can be divided into two major morphological classes: bipolar and multipolar, which have two or more long, aspiny or sparsely spiny dendrites that extend through several layers. In addition, there are unclassified immunopositive neurons that have large lightly stained somata. They are located primarily in layer V. Colocalization analyses with GAD and GABA revealed that approximately 40% (657 out of 1,777) of all calretinin-IR cells within the entorhinal cortex contain GAD or GABA. In layers I-III, over 90% of the calretinin-IR neurons contain GAD or GABA. In layers V-VI, however, most of the calretinin-IR neurons do not colocalize with either GAD or GABA. The distribution patterns of calretinin-immunoreactivity in the entorhinal cortex is consistent with the partitioning of the rat entorhinal cortex into six subfields. Furthermore, calretinin is expressed in a morphologically heterogeneous population of cells in the rat entorhinal cortex which includes both GABAergic and non-GABAergic neurons.

Animals↗
PubMed1997

Seizure-induced damage to somatostatin-immunoreactive neurons in the rat hippocampus is regulated by fimbria-fornix transection.

In both experimental and human temporal lobe epilepsy, seizures cause loss of hilar somatostatin-immunoreactive (SOM-ir) neurons and sprouting of mossy fibers. To investigate whether in rats these alterations are modulated by hippocampal input projections, we transected the fimbria-fornix or the perforant pathway bilaterally 2 days after seizures induced by systemic administration of kainic acid (9 mg/kg, i.p.). Two months later, the number of SOM-ir neurons in the hilus was counted and mossy fiber sprouting in the supragranular area and in the inner molecular layer was analyzed. In seizured rats with sham-operation, 50% of the hilar SOM-ir neurons were left in the septal end of the hippocampus and only 16% remained in the temporal end. In seizured rats with transection of the fimbria-fornix, the number of hilar SOM-ir neurons in the septal end of the hippocampus did not differ from that in controls (98% of SOM-ir neurons left). However, the temporal end was severely damaged (41% of SOM-ir neurons left). In seizured rats with transection of the perforant pathway, 61% of the hilar SOM-ir neurons were left in the septal end and 51% in the temporal end of the hippocampus. Mossy fiber sprouting was evident throughout the septotemporal axis of the hippocampus in all seizured rats. Our results suggest that in the septal end of the hippocampus the severity of neuronal damage in the hilus is modulated by mechanism(s) that are dependent on the afferent pathways entering the hippocampus via the fimbria-fornix. Transection of the fimbria-fornix, however, does not significantly modulate the severity or the target regions of seizure-induced sprouting of mossy fibers.

Animals↗
PubMed1997

Organization of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala.

The amygdala is located in the medial aspects of the temporal lobe. In spite of the fact that the amygdala has been implicated in a variety of functions, ranging from attention to memory to emotion, it has not attracted neuroscientists to the same extent as its laminated neighbours, in particular the hippocampus and surrounding cortex. However, recently, principles of information processing within the amygdala, particularly in the rat, have begun to emerge from anatomical, physiological and behavioral studies. These findings suggest that after the stimulus enters the amygdala, the highly organized intra-amygdaloid circuitries provide a pathway by which the representation of a stimulus becomes distributed in parallel to various amygdaloid nuclei. As a consequence, the stimulus representation may become modulated by different functional systems, such as those mediating memories from past experience or knowledge about ongoing homeostatic states. The amygdaloid output nuclei, especially the central nucleus, receive convergent information from several other amygdaloid regions and generate behavioral responses that presumably reflect the sum of neuronal activity produced by different amygdaloid nuclei.

Amygdala↗
PubMed1997

Interamygdaloid projections of the basal and accessory basal nuclei of the rat amygdaloid complex.

Previous studies suggest that the left and right amygdalae are interconnected in rodents. The origin and topography of these connections have, however, remained obscure. In the present study, we investigated the interamygdaloid projections originating in the different divisions of the basal and accessory basal nuclei of the rat amygdala by using the Phaseolus vulgaris leucoagglutinin anterograde tract-tracing technique. The basal nucleus gave rise to substantial interamygdaloid projections. However, the density of the projections depended on the location of Phaseolus vulgaris leucoagglutinin injection in the basal nucleus. The magnocellular and intermediate divisions projected heavily to the homonymous regions on the contralateral side, as well as to the nucleus of the lateral olfactory tract. The parvicellular division projected lightly to the homonymous region on the contralateral side, to the contralateral anterior amygdaloid area and to the medial division of the central nucleus. The contralateral projections originating in the accessory basal nucleus were light compared to those of the basal nucleus. These data indicate that interamygdaloid connections in the rat brain are extensive and topographically organized. Via these connections, one amygdala may rapidly activate the contralateral side. This may explain, for example, why the epileptic seizures in one amygdala spread contralaterally and cause the development of independent seizure activity in kindling model of temporal lobe epilepsy.

Amygdala↗
PubMed1997

Lateral nucleus of the rat amygdala is reciprocally connected with basal and accessory basal nuclei: a light and electron microscopic study.

Information flow within the intra-amygdaloid circuitry has been generally believed to be unidirectional rather than reciprocal, in which case sensory inputs entering the amygdala via the lateral nucleus would not be modulated by inputs from other amygdaloid regions. In the present study we extend our earlier findings which indicated that the lateral nucleus of the rat amygdala is reciprocally connected with the basal and accessory basal nuclei. The type of synaptic contacts made by these connections is also characterized at the ultrastructural level. An anterograde tracer, Phaseolus vulgaris leucoagglutinin, was injected into the basal (n=22) or accessory basal nuclei (n=12) of the rat amygdala. The results demonstrate that the ventrolateral division of the lateral nucleus receives projections from the basal nucleus, while the medial division receives projections from the accessory basal nucleus. Electron microscopic analyses revealed that axons projecting from the basal nucleus formed both asymmetric and symmetric contacts within the ventrolateral division of the lateral nucleus, whereas axons projecting from the accessory basal nucleus to the medial division of the lateral nucleus formed only asymmetric synapses with their targets. These findings suggest that the lateral nucleus receives both inhibitory and excitatory intra-amygdaloid projections and indicate that information flow within the amygdala is not unidirectional as previously thought. The results of this study provide evidence that the early phase of sensory processing within the amygdala is already modified by inputs from other amygdaloid nuclei.

Amygdala↗
PubMed1997

Cholinergic deafferentation exacerbates seizure-induced loss of somatostatin-immunoreactive neurons in the rat hippocampus.

The loss of somatostatin-immunoreactive neurons and the sprouting of mossy fibers are typical histopathological abnormalities in the hippocampus in experimental and human temporal lobe epilepsy. To investigate whether the development of seizure-induced alterations is regulated by the subcortical afferent pathways to the hippocampus, we lesioned cholinergic, noradrenergic or serotonergic afferent pathways in rats two days after seizures were induced with kainate. Two months later, somatostatin-immunoreactive neurons were counted in the hilus to assess the severity of neuronal damage. Mossy fiber sprouting was analysed from adjacent Timm-stained sections. Kainate-induced seizures caused a loss of hilar somatostatin-immunoreactive neurons in the septal end of the hippocampus, where 63% of the somatostatin-immunoreactive neurons survived. Even more severe damage was found in the temporal end of the hippocampus (only 21% surviving). Cholinergic deafferentation of the hippocampus (using 192-IgG saporin) decreased the overall number of hilar somatostatin-immunoreactive neurons. In control rats that did not receive kainate, 87% (septal end) and 74% (temporal end) of the hilar somatostatin-immunoreactive neurons remained after cholinergic deafferentation. Moreover, seizure-induced damage to hilar somatostatin-immunoreactive neurons was further exacerbated by 192-IgG-saporin, with only 35% of the neurons remaining in the septal end and 14% in the temporal end of the hippocampus. Noradrenergic [using N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] or serotonergic (using 5,7-dihydroxytryptamine) lesions did not affect the number of hilar somatostatin-immunoreactive neurons either in control or in kainate-treated rats. The severity and distribution of seizure-induced mossy fiber sprouting were also not affected by any of the lesions. These data suggest that various subcortical afferent pathways may differentially modulate seizure-induced damage to the hippocampus. Damage to cholinergic neurons results in the loss of hilar somatostatin-immunoreactive neurons and exacerbates the seizure-induced loss of somatostatin-immunoreactive neurons.

Afferent Pathways↗
PubMed1997

Decrease in somatostatin-immunoreactive neurons in the rat amygdaloid complex in a kindling model of temporal lobe epilepsy.

In human temporal lobe epilepsy, seizures can begin in the hippocampus, amygdala, or surrounding cortical areas. Histologically, the seizure-induced selective neuronal damage and synaptic reorganization are best documented in the hippocampus. Little information is available about the damage in the other temporal lobe structures or whether the distribution of damage depends on the location of the primary seizure focus. We used an amygdala-kindling model of temporal lobe epilepsy to study whether seizures of amygdaloid origin cause damage to the amygdala and hippocampus. All rats experienced five class 5 generalized seizures. Neuronal damage was assessed by counting the density of GABA-immunoreactive (GABA-ir) and somatostatin-immunoreactive (SOM-ir) neurons in the amygdala and hilus of the dentate gyrus six months after the last seizure. We found that the density of GABA-ir neurons did not differ from that in controls in the contralateral amygdala. The density of SOM-ir neurons was, however, decreased in the lateral (69% of neurons remaining, P < 0.01), basal (67% remaining, P < 0.05), and accessory basal (68% remaining, P < 0.05) nuclei. In the hilus, the densities of GABA-ir and SOM-ir neurons were similar to that in controls. According to our data, a few seizures of amygdaloid origin may cause more severe damage to SOM-ir neurons in the amygdala than in the hilus. Such decrease in SOM-ir neurons which form one subpopulation of GABAergic inhibitory interneurons may increase the local excitability in the amygdala and, therefore, contribute to epileptogenesis.

Amygdala↗
PubMed1997

MRI volumetry and T2 relaxometry of the amygdala in newly diagnosed and chronic temporal lobe epilepsy.

Little is known about the appearance and severity of amygdaloid damage in temporal lobe epilepsy, particularly in its early stages. In the present magnetic resonance imaging study, we measured amygdaloid volumes and T2 relaxation times in 29 patients with newly diagnosed and in 54 patients with chronic temporal lobe epilepsy. The control population included 25 normal subjects. In the newly diagnosed patients, the mean amygdaloid volume did not differ from that in controls. Also, in the chronic patients the mean amygdaloid volume did not differ from that in controls or in newly diagnosed patients. However, in 19% of the chronic patients the amygdaloid volume was reduced by at least 20%. Moreover, in all of the epilepsy patients, both chronic and newly diagnosed, we found an inverse correlation between the number of epileptic seizures the patient had experienced and the amygdaloid volume on the focal side (focus on the left, r = -0.371, P < 0.01; focus on the right, r = -0.348, P < 0.05). The mean T2 relaxation time in newly diagnosed or chronic patients did not differ from each other or from control values. However, the T2 relaxation time of the left amygdala was > or = 111 msec (i.e., > or = 2 S.D. over the mean T2 time of the left amygdala in control subjects) in seven (10%) patients, one of which was newly diagnosed and six were chronic. The T2 time of the right amygdala was prolonged in eight (12%) patients, three of which were newly diagnosed and five were chronic. We did not find any clear asymmetries in amygdaloid volumes or T2 relaxation times between the ipsilateral and contralateral sides relative to seizure focus. According to the present findings, signs of amygdaloid damage were observed in approximately 20% of patients with temporal lobe epilepsy, most of which had chronic epilepsy.

Adolescent↗
PubMed1996

Parvalbumin-immunoreactive neurons make inhibitory synapses on pyramidal cells in the human amygdala: a light and electron microscopic study.

In the present study we investigate the inhibitory circuitries that regulate the neuronal activity in the lateral and basal nuclei, which are the main sensory input regions of the amygdala. Axon terminals immunoreactive for parvalbumin, a calcium-binding protein known to colocalize with GABA, were examined in these regions with electron microscopy, and their postsynaptic targets were identified and characterized. In the lateral nucleus, parvalbumin-immunoreactive (PV-ir) axons formed terminal rows which made symmetric synaptic contacts on the axon initial segments of the pyramidal cells. In the basal nucleus, pericellular baskets of PV-ir fibers established symmetric synapses on pyramidal cell somata and proximal dendrites. Our data suggest that PV-ir neurons play a crucial inhibitory role in the control of pyramidal cell activity in the human amygdala.

Adult↗
PubMed1996

Intrinsic connections of the rat amygdaloid complex: projections originating in the accessory basal nucleus.

The amygdaloid complex plays an important role in the detection of emotional stimuli, the generation of emotional responses, the formation of emotional memories, and perhaps other complex associational processes. These functions depend upon the flow of information through intricate and poorly understood circuitries within the amygdala. As part of an ongoing project aimed at further elucidating these circuits, we examined the intra-amygdaloid connections of the accessory basal nucleus in the rat. In addition, we examined connections of the anterior cortical nucleus and amygdalahippocampal area to determine whether portions of these nuclei should be included in the accessory basal nucleus (as some earlier studies suggest). Phaseolus vulgaris leucogglutinin was injected into different rostrocaudal levels of the accessory basal nucleus (n = 12) or into the anterior cortical nucleus (n = 3) or amygdalahippocampal area (n = 2). The major intra-amygdaloid projections from the accessory basal nucleus were directed to the medial and capsular divisions of the central nucleus, the medial division of the amygdalohippocampal area, the medial division of the lateral nucleus, the central division of the medial nucleus, and the posterior cortical nucleus. The projections originating in the anterior cortical nucleus and the lateral division of the amygdalohippocampal area differed from those originating in the accessory basal nucleus, which suggests that these areas are not part of the accessory basal nucleus. The present findings and our previous data suggest that each of the deep amygdaloid nuclei have different intra-amygdaloid connections. The pattern of these various connections suggests that information entering the amygdala from different sources can be integrated only in certain amygdaloid regions.

Amygdala↗
PubMed1996

Seizure-induced damage to the hippocampus is prevented by modulation of the GABAergic system.

A variety of cerebral insults induce neuronal damage to the hippocampal formation. The somatostatin-immunoreactive (SOM-ir) neurones in the dentate hilus are particularly vulnerable. In the present study, we demonstrated that augmentation of hippocampal GABAergic inhibition by chronic infusion of gamma-vinyl GABA prevented the delayed seizure-induced damage to hilar SOM-ir neurones. Selective lesions of the cholinergic, serotonergic or noradrenergic pathways to the hippocampus did not attenuate the seizure-induced loss of SOM-ir neurones; rather, the damage was exacerbated by the cholinergic lesion. It is, therefore, the intrahippocampal GABAergic circuitries, rather than the selective subcortical pathways, that are critical for neuroprotection after seizures. Enhanced GABAergic inhibition in the hippocampus prevented damage to hilar SOM-ir neurones, even when started 2 days after status epilepticus. GABAergic agents may thus provide an alternative treatment for delayed neuronal damage caused by cerebral insults.

Animals↗