Sherry L. Feig

A new subdivision of anterior piriform cortex and associated deep nucleus with novel features of interest for olfaction and epilepsy.

The anterior part of the piriform cortex (the APC) has been the focus of cortical‐level studies of olfactory coding and associative processes and has attracted considerable attention as a result of a unique capacity to initiate generalized tonic‐clonic seizures. Based on analysis of cytoarchitecture, connections, and immunocytochemical markers, a new subdivision of the APC and an associated deep nucleus are distinguished in the rat. As a result of its ventrorostral location in the APC, the new subdivision is termed the APCVR. The deep nucleus is termed the pre‐endopiriform nucleus (pEn) based on location and certain parallels to the endopiriform nucleus. The APCVR has unique features of interest for normal function: immunostaining suggests that it receives input from tufted cells in the olfactory bulb in addition to mitral cells, and it provides a heavy, rather selective projection from the piriform cortex to the ventrolateral orbital cortex (VLO), a prefrontal area where chemosensory, visual, and spatial information converges. The APCVR also has di‐ and tri‐synaptic projections to the VLO via the pEn and the submedial thalamic nucleus. The pEn is of particular interest from a pathological standpoint because it corresponds in location to the physiologically defined “deep piriform cortex” (“area tempestas”) from which convulsants initiate temporal lobe seizures, and blockade reduces ischemic damage to the hippocampus. Immunostaining revealed novel features of the pEn and APCVR that could alter excitability, including a near‐absence of γ‐aminobutyric acid (GABA)ergic “cartridge” endings on axon initial segments, few cholecystokinin (CCK)‐positive basket cells, and very low γ‐aminobutyric acid transporter‐1 (GAT1)‐like immunoreactivity. Normal functions of the APCVR‐pEn may require a shaping of neuronal activity by inhibitory processes in a fashion that renders this region susceptible to pathological behavior. J. Comp. Neurol. 434:289–307, 2001.

Immunocytochemical Analysis of Basket Cells in Rat Piriform Cortex

Basket cells, defined by axons that preferentially contact cell bodies, were studied in rat piriform (olfactory) cortex with antisera to γ‐aminobutyric acid (GABA)ergic markers (GABA, glutamate decarboxylase) and to peptides and calcium binding proteins that are expressed by basket cells. Detailed visualization of dendritic and axonal arbors was obtained by silver‐gold enhancement of staining for vasoactive intestinal peptide (VIP), cholecystokinin (CCK), parvalbumin, and calbindin. Neuronal features were placed into five categories: soma‐dendritic and axonal morphologies, laminar distributions of dendritic and axonal processes, and molecular phenotype. Although comparatively few forms were distinguished within each category, a highly varied co‐expression of features from different categories produced a “combinatorial explosion” in the characteristics of individual neurons. Findings of particular functional interest include: dendritic distributions suggesting that somatic inhibition is mediated by feedforward as well as feedback pathways, axonal variations suggesting a differential shaping of the temporal aspects of somatic inhibition from different basket cells, evidence that different principal cell populations receive input from different combinations of basket cells, and a close association between axonal morphology and molecular phenotype. A finding of practical importance is that light microscopic measurements of boutons were diagnostic for the molecular phenotype and certain morphological attributes of basket cells. It is argued that the diversity in basket cell form in the piriform cortex, as in other areas of the cerebral cortex, reflects requirements for large numbers of specifically tailored inhibitory processes for optimal operation that cannot be met by a small number of rigidly defined neuronal populations. J. Comp. Neurol. 434:308–328, 2001.

Corticocortical communication via the thalamus: Ultrastructural studies of corticothalamic projections from area 17 to the lateral posterior nucleus of the cat and inferior pulvinar nucleus of the owl monkey

Electron microscopic anterograde autoradiography has been used to analyze the morphology and postsynaptic relationships of area 17 cortical terminals in the lateral division of the lateral posterior nucleus (LPl) of the cat and medial division of the inferior pulvinar nucleus (IPm) of the owl monkey. Such terminals are thought to arise exclusively from layer 5 in the cat and primate (Lund et al. [1975] J. Comp. Neurol. 164:287–304; Abramson and Chalupa [1985] Neuroscience 15:81–95). All labeled terminals in both nuclei exhibited the morphology of ascending “lemniscal” afferents. That is, they contained round vesicles, were large, made asymmetrical synaptic and filamentous nonsynaptic contacts, and were classified as RLs. These cortical RLs also exhibited the postsynaptic relationships of lemniscal afferents. Thus, they were presynaptic to large dendrites within glial encapsulated glomeruli, where a majority was involved in complex synaptic arrangements called triads. They also were found adjacent to terminal profiles with pleomorphic vesicles but never adjacent to small terminals containing round vesicles.

Connections of higher order visual relays in the thalamus: A study of corticothalamic pathways in cats

Axonal markers injected into layers 5 and 6 of cortical areas 17, 18, or 19 labeled axons going to the lateral geniculate nucleus (LGN), the lateral part of the lateralis posterior nucleus (LPl), and pulvinar (P). Area 19 sends fine axons (type 1, Guillery [ 1966 ] J Comp Neurol 128:21–50) to LGN, LPl, and P, and thicker, type 2 axons to LPl and P. Areas 17 and 18 send type 1 axons to LGN, and a few type 1, but mainly type 2 axons to LPl and P. Type 1 and 2 axons from a single small cortical locus distribute to distinct, generally nonoverlapping parts of LP and P; type 1 axons have a broader distribution than type 2 axons. Type 2 axons, putative drivers of thalamic relay cells (Sherman and Guillery [ 1998 ] Proc Natl Acad Sci USA 95:7121–7126; Sherman and Guillery [ 2001 ] Exploring the thalamus. San Diego: Academic Press), supply small terminal arbors (100‐ to 200‐μm diameter) in LPl and P, and then continue into the midbrain. Each thalamic type 2 arbor contains two terminal types. One, at the center of the arbor, is complex and multilobulated; the other, with a more peripheral distribution, is simpler and may contribute to adjacent arbors. Type 2 arbors from a single injection are scattered around and along “isocortical columns” in LPl, (i.e., columns that represent cells having connections to a common cortical locus). Evidence is presented that the connections and consequently the functional properties of cells in LP change along these isocortical columns. Type 2 driver afferents from a single cortical locus can, thus, be seen as representing functionally distinct, parallel pathways from cortex to thalamus. J. Comp. Neurol. 438:66–85, 2001.

Cortical somatosensory and trigeminal inputs to the cat superior colliculus: Light and electron microscopic analyses

Two different axonal transport tracers were used in single animals to test the hypothesis that the expansive intermediate gray layer of the cat superior colliculus (stratum griseum intermediale, SGI) is composed of sensorimotor domains. The results show that two sensory pathways, the trigeminotectal and the corticotectal arising from the fourth somatosensory area, commingle in patches across the middle tier of the SGI. Furthermore, the data reveal that tectospinal cells are distributed within these patches. Taken together, these results show a commingling of functionally related afferents and a consistent spatial relationship between these afferents and tectospinal neurons. These relationships indicate that the SGI consists of domains that can be distinguished by their unique combinations of afferent and efferent connections. The ultrastructural characteristics and synaptic relationships of these somatosensory afferent pathways suggest that they have distinct roles within the sensorimotor domain of the SGI. The trigeminotectal terminals are relatively small, contain round vesicles and make asymmetrical synapses on small, presumably distal, dendrites. We submit that these trigeminal terminals bestow the basic receptive field properties upon SGI neurons. In contrast, the somatosensory corticotectal terminals are relatively large, contain round vesicles, make asymmetrical synapses, participate in triads, and are presynaptic to proximal dendrites. We suggest that these cortical terminals bestow integrative abilities on SGI neurons. J. Comp. Neurol. 388:313–326, 1997.

Cellular and subcellular localization of Kir2.1 subunits in neurons and glia in piriform cortex with implications for K+ spatial buffering.

Potassium channels of the Kir2 family are widely expressed in neurons and glia, where they form strong inwardly rectifying channels. Existing functional hypotheses for these channels in neurons are based on the weak outward conductance, whereas the leading hypothesis for glia, that they promote potassium spatial buffering, is based on inward conductance. Although the spatial buffering hypothesis has been confirmed for Müller glia in retina, many aspects of Kir2 channels that will be required for understanding their functional roles in neurons and other forms of glia have received little or no study. Particularly striking is the paucity of data regarding their cellular and subcellular localization. We address this gap for Kir2.1‐containing channels by using light and electron microscopic immunocytochemistry. The analysis was of piriform cortex, a highly epileptogenic area of cerebral cortex, where pyramidal cells have K+‐selective strong inward rectification like that observed in Müller cells, where Kir2.1 is the dominant Kir2 subunit. Pyramidal cells in adult piriform cortex also lack Ih, the mixed Na+‐K+ current that mediates a slower form of strong inward rectification in large pyramidal cells in neocortex and hippocampus. The experiments demonstrated surface expression of Kir2.1‐containing channels in astrocytes and in multiple populations of pyramidal and nonpyramidal cells. Findings for astrocytes were not consistent with predictions for K+ spatial buffering over substantial distance. However, findings for pyramidal cells suggest that they could be a conduit for spatially buffering K+ when it is highly elevated during seizure. J. Comp. Neurol. 506:877–893, 2008.

Laminar and cellular targets of individual thalamic reticular nucleus axons in the lateral geniculate nucleus in the prosimian primate Galago.

The visual sector of the thalamic reticular nucleus is the source of the primary inhibitory projection to the visual thalamic relay nucleus, the dorsal lateral geniculate nucleus. The purpose of this study was to investigate laminar and cellular targets of individual thalamic reticular nucleus axons in the highly laminated lateral geniculate nucleus of the prosimian primate Galago to better understand the nature and function of this projection. Thalamic reticular axons labeled anterogradely by means of biotinylated dextran amine were examined by using light microscopic serial reconstruction and electron microscopic analysis in combination with postembedding immunohistochemical labeling for the neurotransmitter γ‐aminobutyric acid (GABA). The synaptic targets of labeled reticular terminal profiles were primarily GABA‐negative dendrites (79–84%) of thalamocortical cells, whereas up to 16% were GABA‐positive dendritic shafts or F2 terminals of interneurons. Reconstructed thalamic reticular nucleus axons were narrowly aligned along a single axis perpendicular to the geniculate laminar plane, exhibiting a high degree of visuotopic precision. Individual reticular axons targeted multiple or all geniculate laminae, with little laminar selectivity in the distribution of swellings with regard to the eye of origin or to the parvocellular, koniocellular, or magnocellular type neurons contained in the separate layers of the Galago lateral geniculate nucleus. These results suggest that cells in the visual thalamic reticular nucleus influence the lateral geniculate nucleus retinotopically, with little regard to visual functional streams. J. Comp. Neurol. 458:128–143, 2003.

Ultrastructural studies of the primate parabigeminal nucleus: electron microscopic autoradiographic analysis of the tectoparabigeminal projection in Galago crassicaudatus ☆

The normal ultrastructure of the parabigeminal nucleus and the morphology and synaptic relationships of tectoparabigeminal terminals have been examined. Five different morphological types of terminals have been observed within the parabigeminal nucleus. Three of these profiles contain round vesicles and make asymmetrical synapses, while two contain pleomorphic vesicles and make symmetrical synapses. Electron microscopic autoradiographic data indicate that labeled tectoparabigeminal terminals represent only one of the three profiles containing round vesicles. Such terminals are primarily presynaptic to dendritic shafts, and several labeled profiles have been observed presynaptic to the same dendrite.

Corticothalamic cells in layers 5 and 6 of primary and secondary sensory cortex express GAP-43 mRNA in the adult rat

The expression of a presynaptic phosphoprotein, growth‐associated protein (GAP)‐43, is associated with synaptogenesis during development and synaptic remodeling in the adult. This study examined GAP‐43 mRNA expression and distribution in primary and secondary areas of visual, auditory, and somatosensory cortex of the adult rat, by in situ hybridization with a digoxigenin‐coupled mRNA probe, focusing particularly on the corticothalamic cells in layers 5 and 6. In the six cortical areas studied, GAP‐43 mRNA was expressed predominantly in layers 5 and 6 and was greater in secondary than primary areas. There were densely labeled cells in layers 5 and 6 of all areas, which showed a restricted sublaminar distribution in primary areas and more even distribution in secondary areas. Combining retrograde transport of rhodamine beads with in situ hybridization in visual and auditory cortex showed that corticothalamic cells in layers 5 and 6 express GAP‐43 mRNA. There are more of these GAP‐43 mRNA positive corticothalamic cells in layer 5 of secondary areas than in primary areas. The evidence suggests that in the adult rat, plasticity related to GAP‐43 is present in primary and secondary sensory cortex and more so in secondary areas. J. Comp. Neurol. 468:96–111, 2004.

Surface‐associated astrocytes, not endfeet, form the glia limitans in posterior piriform cortex and have a spatially distributed, not a domain, organization

“Surface‐associated astrocytes” (SAAs) in posterior piriform cortex (PPC) are unique by virtue of a direct apposition to the cortical surface and large‐caliber processes that descend into layer I. In this study additional unique and functionally relevant features of SAAs in PPC of the rat were identified by light and electron microscopy. Examination of sections cut parallel to the surface of PPC and stained for glial fibrillar acidic protein revealed that, in addition to descending processes, SAAs give rise to an extensive matrix of “superficial processes.” Electron microscopy revealed that these superficial processes, together with cell bodies, form a continuous sheet at the surface of PPC with features in common with the glia limitans that is formed by endfeet in other cortical areas. These include a glia limiting membrane with basal lamina and similar associated organelles, including a striking array of mitochondria. Of particular interest, SAAs lack the domain organization observed in neocortex and hippocampus. Rather, superficial processes overlap extensively with gap junctions between their proximal regions as well as between cell bodies. Study of the descending processes revealed thin extensions, many of which appose synaptic profiles. We conclude that SAAs provide a potential substrate for bidirectional signaling and transport between brain and the pial arteries and cerebrospinal fluid in the subarachnoid space. We postulate that the spatially distributed character of SAAs in PPC reflects and supports the spatially distributed circuitry and sensory representation that are also unique features of this area. J. Comp. Neurol. 519:1952–1969, 2011.