Associational connections of pyramidal cells in rat posterior piriform cortex were studied by direct visualization of axons stained by intracellular injection in vivo. The results revealed that individual cells have widespread axonal arbors that extend over nearly the full length of the cerebral hemisphere. Within piriform cortex these arbors are highly distributed with no regularly arranged patchy concentrations like those associated with the columnar organization in other primary sensory areas (i.e., where periodically arranged sets of cells have common response properties, inputs, and outputs). A lack of columnar organization was also indicated by a marked disparity in the intrinsic projection patterns of neighboring injected cells. Analysis of axonal branching patterns, bouton distributions, and dendritic arbors suggested that each pyramidal cell makes a small number of synaptic contacts on a large number (Ͼ1000) of other cells in piriform cortex at disparate locations. Axons from individual pyramidal cells also arborize extensively within many neighboring cortical areas, most of which send strong projections back to piriform cortex. These include areas involved in high-order functions in prefrontal, amygdaloid, entorhinal, and perirhinal cortex, to which there are few projections from other primary sensory areas. Our results suggest that piriform cortex performs correlative functions analogous to those in association areas of neocortex rather than those typical of primary sensory areas with which it has been traditionally classed. Findings from other studies suggest that the olfactory bulb subserves functions performed by primary areas in other sensory systems. Key words: piriform cortex; olfactory cortex; cortico-cortical; olfaction; association cortex; neural networksPiriform cortex has long been considered as "primary" olfactory cortex because it is the largest area that receives direct input from the olfactory bulb (OB), the structure that monosynaptically relays input from olfactory receptor neurons. However, physiological and anatomical studies suggest that this cortical area is organized in a fundamentally different way than the primary cortical areas for nonchemical senses (Haberly, 1998). Physiological studies have shown that neurons in piriform cortex typically respond in varying degree to odorant molecules with a broad range of structure (Tanabe et al., 1975;Schoenbaum and Eichenbaum, 1995), in contrast to the exquisite selectivity exhibited by cells in primary sensory areas in neocortex. Studies with extracellularly injected axon tracers have shown that associational (cortico-cortical) projections from restricted regions of piriform cortex are highly distributed spatially, both within piriform cortex and in other olfactory cortical areas (Haberly and Price, 1978;Luskin and Price, 1983). This contrasts with the topographically ordered, columnar architecture of the other primary sensory areas in rat and higher mammals (Chapin et al., 1987;Malach, 1989;Ojima et al., 1991), and is reminiscent of so-...

The multisubunit (␣ 1S , ␣ 2 ͞␦, ␤ 1 , and ␥) skeletal muscle dihydropyridine receptor transduces transverse tubule membrane depolarization into release of Ca 2؉ from the sarcoplasmic reticulum, and also acts as an L-type Ca 2؉ channel. The ␣ 1S subunit contains the voltage sensor and channel pore, the kinetics of which are modified by the other subunits. To determine the role of the ␤ 1 subunit in channel activity and excitation-contraction coupling we have used gene targeting to inactivate the ␤ 1 gene. ␤ 1 -null mice die at birth from asphyxia. Electrical stimulation of ␤ 1 -null muscle fails to induce twitches, however, contractures are induced by caffeine. In isolated ␤ 1 -null myotubes, action potentials are normal, but fail to elicit a Ca 2؉ transient. L-type Ca 2؉ current is decreased 10-to 20-fold in the ␤ 1 -null cells compared with littermate controls. Immunohistochemistry of cultured myotubes shows that not only is the ␤ 1 subunit absent, but the amount of ␣ 1S in the membrane also is undetectable. In contrast, the ␤ 1 subunit is localized appropriately in dysgenic, mdg͞mdg, (␣ 1S -null) cells. Therefore, the ␤ 1 subunit may not only play an important role in the transport͞insertion of the ␣ 1S subunit into the membrane, but may be vital for the targeting of the muscle dihydropyridine receptor complex to the transverse tubule͞sarcoplasmic reticulum junction.

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 APC(VR). The deep nucleus is termed the pre-endopiriform nucleus (pEn) based on location and certain parallels to the endopiriform nucleus. The APC(VR) 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 APC(VR) 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 APC(VR) that could alter excitability, including a near-absence of gamma-aminobutyric acid (GABA)ergic "cartridge" endings on axon initial segments, few cholecystokinin (CCK)-positive basket cells, and very low gamma-aminobutyric acid transporter-1 (GAT1)-like immunoreactivity. Normal functions of the APC(VR)-pEn may require a shaping of neuronal activity by inhibitory processes in a fashion that renders this region susceptible to pathological behavior.

The goal of this study was to identify GABAergic input to the cat superior colliculus from neurons located in the caudal diencephalon, mesencephalon, pons and medulla. Cells efferent to the superior colliculus were labeled retrogradely with the tracer horseradish peroxidase, and an antibody to gamma-aminobutyric acid was used to label GABAergic neurons in the same sections. The results indicate that neurons in several distinct areas of the caudal diencephalon and brainstem are both immunocytochemically labeled for GABA and retrogradely labeled with horseradish peroxidase. These areas include zona incerta, nucleus of the posterior commissure, anterior and posterior pretectal nuclei, nucleus of the optic tract, superior colliculus, cuneiform nucleus, subcuneiform area, substantia nigra pars reticulata and pars lateralis, periparabigeminal area, external nucleus of the inferior colliculus, the area ventral to the external nucleus of the inferior colliculus, mesencephalic reticular formation, dorsal and ventral nuclei of the lateral lemniscus, and the perihypoglossal nucleus. The role that such diverse inhibitory input to the superior colliculus might play, particularly in influencing eye movements, is discussed.

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