Biomedical subjects

Martha E Bickford

Publications and source records attributed to Martha E Bickford.

15 recordsLinked to original sources

PubMed2006

Comparison of the ultrastructure of cortical and retinal terminals in the rat superior colliculus.

We compared the ultrastructure and synaptic targets of terminals of cortical or retinal origin in the stratum griseum superficiale and stratum opticum of the rat superior colliculus. Following injections of biotinylated dextran amine into cortical area 17, corticotectal axons were labeled by anterograde transport. Corticotectal axons were of relatively small caliber with infrequent small varicosities. At the ultrastructural level, corticotectal terminals were observed to be small profiles (0.44 +/- 0.27 microm(2)) that contained densely packed round vesicles. In tissue stained for gamma amino butyric acid (GABA) using postembedding immunocytochemical techniques, corticotectal terminals were found to contact small (0.51 +/- 0.69 microm(2)) non-GABAergic dendrites and spines (93%) and a few small GABAergic dendrites (7%). In the same tissue, retinotectal terminals, identified by their distinctive pale mitochondria, were observed to be larger than corticotectal terminals (3.34 +/- 1.79 microm(2)). In comparison to corticotectal terminals, retinotectal terminals contacted larger (1.59 +/- 1.70 microm(2)) non-GABAergic dendrites and spines (73%) and a larger proportion of GABAergic profiles (27%) of relatively large size (2.17 +/- 1.49 microm(2)), most of which were vesicle-filled (71%). Our results suggest that cortical and retinal terminals target different dendritic compartments within the neuropil of the superficial layers of the superior colliculus.

Animals↗

PubMed2005

Ultrastructural analysis of projections to the pulvinar nucleus of the cat. I: Middle suprasylvian gyrus (areas 5 and 7).

The mammalian pulvinar nucleus (PUL) establishes heavy interconnections with the parietal lobe, but the precise nature of these connections is only partially understood. To examine the distribution of corticopulvinar cells in the cat, we injected the PUL with retrograde tracers. Corticopulvinar cells were located in layers V and VI of a wide variety of cortical areas, with a major concentration of cells in area 7. To examine the morphology and distribution of corticopulvinar terminals, we injected cortical areas 5 or 7 with anterograde tracers. The majority of corticopulvinar axons were thin fibers (type I) with numerous diffuse small boutons. Thicker (type II) axons with fewer, larger boutons were also present. Boutons of type II axons formed clusters within restricted regions of the PUL. We examined corticopulvinar terminals labeled from area 7 at the ultrastructural level in tissue stained for gamma-aminobutyric acid (GABA). By correlating the size of the presynaptic and postsynaptic profiles, we were able to quantitatively divide the labeled terminals into two categories: small and large (RS and RL, respectively). The RS terminals predominantly innervated small-caliber non-GABAergic (thalamocortical cell) dendrites, whereas the RL terminals established complex synaptic arrangements with dendrites of both GABAergic interneurons and non-GABAergic cells. Interpretation of these results using Sherman and Guillery's recent theories of thalamic organization (Sherman and Guillery [1998] Proc Natl Acad Sci U S A 95:7121-7126) suggests that area 7 may both drive and modulate PUL activity.

Animals↗

PubMed2005

Ultrastructural analysis of projections to the pulvinar nucleus of the cat. II: Pretectum.

The pretectum (PT) can supply the pulvinar nucleus (PUL), and concomitantly the cortex, with visual motion information through its dense projections to the PUL. We examined the morphology and synaptic targets of pretecto-pulvinar (PT-PUL) terminals labeled by anterograde transport in the cat. By using postembedding immunocytochemical staining for gamma-aminobutyric acid (GABA), we additionally determined whether PT-PUL terminals or their postsynaptic targets were GABAergic. We found that the main projection from the PT to the PUL is an ipsilateral, non-GABAergic projection (72.4%) that primarily contacts thalamocortical cell dendrites (87.6%), and also the dendritic terminals of interneurons (F2 profiles; 12.4%). The PT additionally provides GABAergic innervation to the PUL (27.6% of the ipsilateral projection), which chiefly contacts relay cell dendrites (84.6%) but also GABAergic profiles (15.4%). These GABAergic pretectal terminals are smaller, beaded fibers that likely branch to bilaterally innervate the PUL and dLGN, and possibly other targets. We also examined the neurochemical nature of PT-PUL cells labeled by retrograde transport and found that most are non-GABAergic cells (79%) and devoid of calbindin. Taking existing physiological and our present morphological data into account, we suggest that, in addition to the parietal cortex, the non-GABAergic PT-PUL projection may also strongly influence PUL activity. The GABAergic pretectal fibers, however, may provide a more widespread influence on thalamic activity.

Afferent Pathways↗

PubMed2005

Cortical function: a view from the thalamus.

Neuroscientists from across the country gathered at the University of Wisconsin, Madison in September to honor Ray Guillery and his seminal work on the thalamus. The meeting focused on three timely research topics, each of which inspired new thinking about thalamic function. Presentations on the organization and dynamic nature of thalamocortical pathways, the role of the thalamus in communication between cortical areas, and the relationship between sensory and motor pathways of the brain, including cognitive aspects of thalamocortical processing, made for lively discussions. The meeting revealed that communication between thalamus and cortex is so rich that we should no longer consider the operations of either structure separately from the other. Proceedings of the meeting will be published in Progress in Brain Research in 2005. In this report, we provide a general overview of the main themes of the meeting.

Animals↗

PubMed2003

Thalamocortical cells in the cat pulvinar nucleus transiently express nitric oxide synthase during development.

We examined the postnatal expression of the neuronal form of nitric oxide synthase (nNOS) within the pulvinar and lateral posterior (LP) nuclei of the cat thalamus using immunocytochemical techniques. During the first postnatal month, nNOS was expressed in many cells within the pulvinar nucleus and medial subdivision of the LP nucleus; fewer neurons in the lateral LP nucleus were stained by the nNOS antibody. We examined the pulvinar nucleus to determine what cell types express nNOS. A comparison of the soma sizes of nNOS-stained cells to the overall population of Nissl-stained cells and interneurons (stained with an antibody against glutamic acid decarboxylase) suggests that within the pulvinar nucleus, thalamocortical cells express nNOS during development. In addition, the nNOS antibody stained axon bundles that traverse the pulvinar nucleus to enter the optic radiations, suggesting that thalamocortical cell axons also contain nNOS during development. However, this staining pattern was dramatically reduced by postnatal day 42 and later ages; the size of the remaining nNOS-stained cells was closer to that of interneurons, a subset of which contain nNOS in the adult pulvinar nucleus. This contrasts with our previous findings that nNOS is specifically expressed within interneurons in the developing dorsal lateral geniculate nucleus (LGN) and serves as further confirmation that the pulvinar nucleus and LGN represent distinct categories of thalamic nuclei.

Animals↗

PubMed2003

Ultrastructure and synaptic targets of tectothalamic terminals in the cat lateral posterior nucleus.

The recent appreciation of the fact that the pulvinar and lateral posterior (LP) nuclei receive two distinct types of cortical input has sparked renewed interest in this region of the thalamus. A key question is whether the primary or "driving" inputs to the pulvinar/LP complex originate in cortical or subcortical areas. To begin to address this issue, we examined the synaptic targets of tectothalamic terminals within the LP nucleus. Tectothalamic terminals were labeled using the anterograde transport of biotinylated dextran amine (BDA) or Phaselous leucoagglutinin placed in the superior colliculus or using immunocytochemical staining for substance P, a neurotransmitter found to be used by the tectothalamic pathway (Hutsler and Chalupa [ 1991] J. Comp. Neurol. 312:379-390). Our results suggest that most tectothalamic terminals are large and occupy a proximal position on the dendritic arbor of LP relay cells. In the medial LP, tectothalamic terminals labeled by the transport of neuronal tracers or substance P immunocytochemistry can form tubular clusters that surround the proximal dendrites of relay cells. In a rostral and lateral subdivision of the lateral LP nucleus (LPl-2), tectothalamic terminals form more typical glomerular arrangements. When compared with existing physiological data, these results suggest that a unique integration of tectal and cortical inputs may contribute to the response properties of LP neurons.

Animals↗

PubMed2003

Pretectotectal pathway: an ultrastructural quantitative analysis in cats.

Both the pretectum (PT) and the superior colliculus (SC) play an important role in directing eye movements and in sensorimotor coupling. A reciprocal connection between the PT and the SC has been described, which suggests a strong interplay between these two structures. We injected the cat SC with retrograde tracers and examined the labeled pretectotectal (PTT) cells at the light and electron microscopic level. PTT cells were distributed mostly in the nucleus of the optic tract and 93.1% contained gamma amino butyric acid (GABA). We also observed that PTT cells are located outside of pretectal regions distinguished by dense retinal terminals and clusters of cells that contain calbindin. This suggests that the GABAergic PTT cells are distinct from the GABAergic pretectogeniculate cells that have been previously described as being distributed within these regions. Finally, to determine the synaptic targets of PTT terminals, we injected the PT with anterograde tracers and examined terminals labeled in the SC at the ultrastructural level. The labeled PTT terminals were beaded fibers that were distributed mainly within the stratum griseum superficiale (SGS) of the SC. Using postembedding immunocytochemistry, 94.5% were found to be GABAergic. The PTT terminals were mostly small in size and primarily contacted GABA-negative dendrites (88.1%) and in some cases somata (4.7%). The remainder terminated on GABAergic dendrites (7.2%). Our results suggest that the PTT cells constitute a separate population of GABAergic efferent cells in the PT, which may function to inhibit the activity of non-GABAergic SC efferent cells in the SGS.

Animals↗

PubMed2003

Two distinct types of corticothalamic EPSPs and their contribution to short-term synaptic plasticity.

The lateral posterior nucleus (LPN) is innervated by two different morphological types of cortical terminals that originate from cortical layers V and VI. Here we describe two distinct types of excitatory postsynaptic potentials (EPSPs) that were recorded in the LPN after stimulation of corticothalamic fibers. These types of EPSPs differed in amplitude, latency, rise time, and response to increasing levels of stimulus intensity. The most frequently encountered EPSP, type I, displayed a longer latency and slower rise time than the less frequently encountered type II EPSP. Type I EPSPs also showed a graded increase in amplitude with increasing levels of stimulation, whereas type II EPSPs showed an all-or-none response. In response to repetitive stimulation (0.5-20 Hz), type I EPSPs displayed frequency-dependent facilitation, whereas type II EPSPs displayed frequency-dependent depression. Further details of these distinct forms of short-term synaptic plasticity were explored using paired-pulse stimuli. Pharmacology experiments revealed that both N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors are involved in corticothalamic synaptic transmission in the LPN and contribute to both synaptic facilitation and depression. Taken together with the results of our previous anatomical studies, these results suggest that type I EPSPs arise from stimulation of layer VI afferents, whereas type II EPSPs arise from stimulation of layer V inputs. Moreover, type I and II EPSPs in the LPN may be functionally similar to corticogeniculate and retinogeniculate EPSPs, respectively.

Animals↗

PubMed2003

Inhibitory circuitry involving Y cells and Y retinal terminals in the C laminae of the cat dorsal lateral geniculate nucleus.

We previously established (Datskovskaia et al. [2001] J Comp Neurol 430:85-100) that roughly 40% of Y retinal terminals contact interneurons in the A lamina of the dorsal lateral geniculate nucleus (dLGN) of the cat. However, we did not establish whether the dendritic terminals of interneurons postsynaptic to Y retinal terminals subsequently contact Y thalamocortical cells. To begin to address this issue, we examined the synaptic targets of Y retinal terminals in the magnocellular C lamina of the dLGN, which is populated almost exclusively by Y thalamocortical cells and interneurons. We utilized material generated from our previous work, in which we injected the superior colliculus with biotinylated dextran amine to backfill the geniculate branches of Y retinogeniculate axons in the dLGN. Sections prepared for electron microscopy were stained for gamma aminobutyric acid (GABA) to distinguish interneurons from thalamocortical cells. We found that the majority of profiles postsynaptic to Y retinal axons were the GABA-negative dendrites of thalamocortical cells (116/200, 58%). The remainder were GABA-positive dendrites of interneurons (84/200, 42%), many of which contained vesicles (F2 profiles; 54/200, 27%). In addition, we examined the synaptic targets of F2 profiles and found that almost all contacts of F2 profiles in the magnocellular C lamina were made onto the GABA-negative dendrites of thalamocortical cells (199/200, 99.5%). Thus, Y retinogeniculate axons contact interneurons and interneurons contact Y thalamocortical cells in the magnocellular C lamina of the dLGN. This indicates that interneurons are involved in modulation of the Y pathway.

Animals↗

PubMed2003

Comparison of the ultrastructure of cortical and retinal terminals in the rat dorsal lateral geniculate and lateral posterior nuclei.

We compared the ultrastructure and synaptic targets of terminals of cortical or retinal origin in the rat dorsal lateral geniculate nucleus (LGN) and lateral posterior nucleus (LPN). Following injections of biotinylated dextran amine (BDA) into cortical area 17, two types of corticothalamic terminals were labeled by anterograde transport. Type I terminals, found throughout the LGN and LPN, were small, drumstick-shaped terminals that extended from thin axons. At the ultrastructural level in both the LGN and LPN, labeled type I corticothalamic terminals were observed to be small profiles that contained densely packed round vesicles (RS profiles) and contacted small-caliber dendrites. In tissue stained for gamma amino butyric acid (GABA) using postembedding immunocytochemical techniques, most dendrites postsynaptic to type I corticothalamic terminals did not contain GABA (97%). Type II corticothalamic terminals, found only in the LPN, were large terminals that sometimes formed clusters. At the ultrastructural level, type II terminals were large profiles that contained round vesicles (RL profiles) and contacted large-caliber dendrites, most of which did not contain GABA (98%). Retinogeniculate terminals, identified by their distinctive pale mitochondria, were similar to type II corticothalamic terminals except that 26% of their postsynaptic targets were vesicle-containing profiles that contained GABA (F2 profiles). Our results suggest that type I corticothalamic terminals are very similar across nuclei but that the postsynaptic targets of RL profiles vary. Comparison of the responses to retinal inputs in the LGN and to layer V cortical inputs in the LPN may provide a unique opportunity to determine the function of interneurons in the modulation of retinal signals and, in addition, may provide insight into the signals relayed by cortical layer V.

Animals↗

PubMed2003

Distinct firing properties of higher order thalamic relay neurons.

It has been proposed that the thalamus is composed of at least two types of nuclei. First-order relay nuclei transmit signals from the periphery to the cortex while higher order nuclei may route information from one cortical area to another. Although much is known about the functional properties of relay neurons in first-order nuclei, little is known about relay neurons belonging to higher-order nuclei. We investigated the electrophysiological properties of relay cells in a higher-order thalamic nucleus using in vitro intracellular recordings from thalamic slices of the rat's lateral posterior nucleus (LPN). We found neurons of the LPN possess many of the same membrane properties as first-order relay neurons. These included low-threshold calcium spikes (IT) and burst firing, a mixed cation conductance (IH) that prevented membrane hyperpolarization, and a transient K+ conductance that delayed spike firing (IA). The repetitive firing characteristics of LPN neurons were more distinct. One group of cells, located in the more caudal regions of the LPN responded to depolarizing current pulses with a train of action potentials or in a regular spiking (RS) mode. This form of firing showed a steep but highly linear increase in firing frequency with increasing levels of membrane depolarization. Another group of cells, located in the more rostral regions of the LPN, responded to depolarizing current pulses with clusters of high-frequency bursts or in a clustered spiking (CS) mode. The overall firing frequency rose nonlinearly with membrane depolarization, but the frequency of a given burst remained relatively constant. The caudal LPN receives input from the superior colliculus, whereas the rostral LPN receives input from layers V and VI of the visual cortex. Thus the RS and CS cells may be driven by subcortical and cortical inputs respectively, and the distinct temporal properties of their response modes may be a necessary component of the LPN circuitry.

Action Potentials↗

PubMed2002

Relative distribution of synapses in the pulvinar nucleus of the cat: implications regarding the "driver/modulator" theory of thalamic function.

To provide a quantitative comparison of the synaptic organization of "first-order" and "higher-order" thalamic nuclei, we followed bias-corrected sampling methods identical to a previous study of the cat dorsal lateral geniculate nucleus (dLGN; Van Horn et al. [2000] J. Comp. Neurol. 416:509-520) to examine the distribution of terminal types within the cat pulvinar nucleus. We observed the following distribution of synaptic contacts: large terminals that contain loosely packed round vesicles (RL profiles), 3.5%; presynaptic profiles that contain densely packed pleomorphic vesicles (F1 profiles), 7.3%; profiles that could be both presynaptic and postsynaptic that contain loosely packed pleomorphic vesicles (F2 profiles), 5.0%; and small terminals that contain densely packed round vesicles (RS profiles), 84.2%. Postembedding immunocytochemistry for gamma-aminobutyric acid (GABA) was used to distinguish the postsynaptic targets as thalamocortical cells or interneurons. The distribution of synaptic contacts on thalamocortical cells was as follows: RL profiles, 2.1%; F1 profiles, 6.9%; F2 profiles, 5.4%; and RS profiles, 85.6%. The distribution of synaptic contacts on interneurons was as follows: RL profiles, 11.8%; F1 profiles, 9.7%; F2 profiles, 2.8%; and RS profiles, 75.6%. These distributions are similar to that found within the dLGN in that the RS inputs (the presumed "modulators") far outnumber the RL inputs (the presumed "drivers"). However, in comparison to the dLGN, the pulvinar nucleus receives significantly fewer numbers of RL, F1, and F2 contacts and significantly higher numbers of RS contacts. Thus, the RS/RL synapse ratio in the pulvinar nucleus is 24:1, in contrast to the 5:1 RS/RL synapse ratio in the dLGN (Van Horn et al., 2000). In first-order nuclei, the lower RS/RL synapse ratio may result in the transfer of visual information that is largely unmodified. In contrast, in higher-order nuclei, the higher RS/RL synapse ratio may allow for a finer modulation of driving inputs.

Animals↗

PubMed2002

GABAergic circuitry in the dorsal division of the cat medial geniculate nucleus.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter of the thalamus. We used postembedding immunocytochemistry to examine the synaptic organization of GABA-positive profiles in the dorsal superficial subdivision of the cat medial geniculate nucleus (MGN). Three groups of GABA-positive profiles participate in synapses: axon terminals, dendrites, and presynaptic dendrites. The presynaptic GABA-positive terminals target mainly GABA-negative dendrites. The GABA-positive postsynaptic profiles receive input primarily from GABA-negative axons. The results indicate that the synaptic organization of GABA-positive profiles in the dorsal superficial subdivision of the MGN nucleus is very similar to that in other thalamic nuclei.

Animals↗

PubMed2002

GABAergic pretectal terminals contact GABAergic interneurons in the cat dorsal lateral geniculate nucleus.

Anterograde tracing techniques combined with postembedding immunocytochemical staining were used to determine the gamma amino butyric acid (GABA) content of pretectogeniculate (PT-LGN) terminals and their postsynaptic targets. The results provide evidence that PT-LGN terminals are GABAergic and that they contact GABAergic interneurons. These results corroborate previous anatomical studies and support the idea that the PT-LGN projection functions to disinhibit thalamocortical cells in the dorsal lateral geniculate nucleus.

Animals↗

PubMedDate not supplied

Synaptic inputs of class III and class V interneurons in the cat pulvinar nucleus: differential integration of RS and RL inputs.

We previously reported that two types of visual thalamic interneurons (class III and class V) could be distinguished by the presence or absence of the enzyme brain nitric oxide synthase (bNOS; Bickford et al., 1999). In the present study, we found that further immunocytochemical characterization can be used to isolate class V and class III neurons: class V neurons express GABA and bNOS but not the calcium binding protein calbindin, whereas class III neurons express GABA and calbindin, but not bNOS. By pairing staining for bNOS or calbindin with staining for GABA, we were able to distinguish class III and class V neurons, thereby allowing us to characterize the synaptic inputs to these two interneuron populations within the cat pulvinar nucleus. We found class III and class V interneurons participate in distinctly different circuitries. Class III cells receive the majority of their input from large terminals with round vesicles (RL profiles, that presumably originate from cortical layer V) while class V cells receive all of their input from small terminals with round vesicles (RS profiles, that presumably originate from cortical layer VI). These two types of interneurons also target different regions of the dendritic arbors of thalamocortical cells; class III cells contact large caliber (presumably proximal) thalamocortical dendrites within glomeruli, while class V cells contact the small caliber (presumably distal) thalamocortical cell dendrites within the extraglomerular neuropil. Thus, a dual inhibitory system exists within the visual thalamus that integrates different types of corticothalamic input and targets distinct regions of thalamocortical cell dendritic arbors.

Animals↗