Olfactory cortex, projections

Fig. 13. Basic olfactory network. Schematic of the networks linking the olfactory bulb and primary olfactory cortex. Olfactory nerve axons (ON) terminate in the glomeruli (glom) onto mitral (m) and tufted (t) cells which project via the lateral olfactory tract (LOT) to layer la of primary olfactory cortex to terminate on the dendrites of layer Il-III pyramidal (p) cells. Layer 11-111 pyramidal cells in rostral olfactory cortex project to layer Ib in caudal olfactory cortex and vice versa. Olfactory cortical pyramidal cells also send reciprocal projections back to the olfactory bulb. Thus olfactory bulb output is continuously modified by feedback from areas it targets. Inhibitory interneurons in olfactory bulb and olfactory cortex (shown in gray) modulate network function. Neurons in the ipsilateral (AONi) and contralateral anterior olfactory nuclei (AON) link olfactory networks in the two hemispheres via the anterior commissure.

Neafsey, E.J., Hurley-Gius, K.M. and Arvanitis, D. (1986) The topographical organization of neurons in the rat medial frontal, insular and olfactory cortex projecting to the solitary nucleus, olfactory bulb, periaqueductal gray and superior colliculus. Brain Res., 377, 261-270. 

Mitral and tufted cells in the olfactory bulb project their axons to the olfactory cortex, the site thought to integrate the signals from distinct glomeruli. The olfactory signals processed in the olfactory cortex are sent to a variety of higher centers of the brain, which include insular cortex, orbitofrontal cortex, amygdale, hippocampus, and the nucleus accumbens.205... 

The basic circuitry of the MOB. Axons of ORNs travel in the ONL and synapse in the GL on the dendrites of mitrai ceiis (MC), tufted ceiis (externai tufted ceii, ET middie tufted ceii, MT), and generic juxtagiomeruiar (JG) neurons, which include perigiomeruiar ceiis (PG), ET ceiis, and short axon ceiis (SA). SA ceiis interconnect different giomeruii. There are serial and reciprocal synapses between the apicai dendrites of mitral/tufted cells and the processes of JG neurons. Superficial tufted cells (ST) are located in the superficial EPL or at the GL-EPL border. The lateral dendrites of mitral/tufted cells form serial and reciprocal synapses with the apical dendrites of granule cells (GC) in the EPL. GCs are located in the GCL and the MCL. The axons of mitral/tufted cells project locally to GCs (not shown) and also to primary olfactory cortex via the lateral olfactory tract (LOT). The bulb also contains other populations of interneurons neurons, including the van Gehuchten cells (VG) within the EPL... 

Major connections of the main olfactory system. Axons of MOB mitral/tufted cells (circles in the EPL and MCL, respectively) project as the LOT to synapse in a number of structures collectively referred to as primary olfactory cortex (POC). Centrifugal inputs to MOB include feedback projections from POC as well as inputs from subcortical forebrain and brainstem neuromodulatory cell groups. Abbreviations AON, anterior olfactory nucleus DP, dorsal peduncular cortex Ent, entorhinal cortex IG-AHC, indusium griseum-anterior hippocampal continuation LC, locus coeruleus NDB, nucleus of the diagonal band PeCo, periamygdaloid cortex PC, piriform cortex RN, raphe nuclei (dorsal and median raphe) TT, taenia tecta Tu, olfactory tubercle... 

Recently, the neuropeptide, corticotropin releasing factor (CRF), has been demonstrated in mitral and some tufted cells using both immunocytochemistry (Fig. 1 IB) and in situ hybridization in the rat (Imaki et al. 1989). CRF fibers were also observed in the molecular layer of the piriform cortex. This finding is consistent with CRF being a releasable neural peptide in mitral cells since mitral cells synaptically terminate in the molecular layer of the piriform cortex. A similar localization of CRF has been reported in the squirrel monkey suggesting that this peptide may be a conserved transmitter/ modulator in the mitral/tufted cells of many mammals (Bassett et al. 1992). Finally, calretinin, a calcium binding protein, has been shown by immunohistochemistry to be localized in mitral cells (Jacobowitz and Winsky, 1991). Transmitter candidates for mitral and tufted cells are discussed further in 2.5.3., Projections to olfactory cortex. 

MOB projects to several structures of the ipsilateral hemisphere, including the superficial plexiform layer of the anterior olfactory nucleus, piriform, periamygdaloid and lateral entorhinal cortices, taenia tecta, the anterior hippocampal continuation, in-dusium griseum and the olfactory tubercle (Figs. 14, 18, 19). Collectively, the regions directly innervated by the output of the MOB have been referred to as primary olfactory cortex (De Olmos et al. 1978). Most of these projections have been reported in several species (for review, cf. Shipley and Adamek, 1984). A recent study has also shown a... 

Fig, 14. Major connections of the main (MOB) and accessory (AOB) bulbs with cortical (gray panels) and subcortical structures (ellipses). Output projections of MOB and AOB shown by solid lines reciprocal and centrifugal projections to MOB and AOB are shown by gray lines. Cortical areas comprising the primary and accessory olfactory cortex are indicated by squares. 

The main olfactory bulb projects to a collection of structures referred to collectively as primary olfactory cortex (De Olmos et al. 1978). These structures may be usefully divided into three groups (A) the anterior olfactory nucleus (Fig. 15) (B) rostral olfac-... 

Luskin and Price (1983b) described additional outputs of the AON including projections to ventral taenia tecta, piriform cortex and olfactory tubercle, endopiriform cortex, ventral agranular insular cortex and nucleus accumbens (from ventroposterior portion of AON). According to Luskin and Price, there are very few projections outside olfactory cortex from AON, although Price et al. (1991) have confirmed a strong projection from AON to the lateral hypothalamus. 

The taenia tecta proper (tt2) projects strongly to the olfactory bulb (De Olmos et al. 1978 Shipley and Adamek, 1984). Haberly and Price (1978b) divided the taenia tecta into dorsal and ventral subdivisions. The ventral subdivision (Fig. 16) has reciprocal connections with the MOB and with parts of the olfactory cortex. The neurons of this cortical... 

The cytoarchitecture of NLOT (Fig. 17C) has been studied extensively by McDonald (1983). It is considered an anterior part of the amygdala. NLOT can be subdivided into 3 layers on the basis of Nissl preparations a superficial plexiform layer I which contains a few small and medium-sized cells, a layer II which contains many tightly packed cells, and layer III located dorsal to layer II and containing fairly large, loosely packed cells. Most cells of NLOT are medium-sized pyramidal shaped with extensive spines on secondary and distal dendrites. According to McDonald (1983), layers I and II appear similar in connections to the piriform cortex while layer III seems to be a closely related subcortical area. Many neurons of layers II and fewer neurons of layer III project to the olfactory bulb (de Olmos et al. 1978 Shipley and Adamek, 1984). In addition to olfactory bulb projections, many axons of NLOT neurons make up the stria terminalis and cross to the contralateral piriform cortex, olfactory tubercle, lateral nucleus of the amygdala, and bed nucleus of the stria terminalis (de Olmos, 1972). Afferent connections to NLOT arise mainly from olfactory related areas and the basolateral nucleus of the amygdala. 

The main olfactory bulb sends a projection to the entire extent of piriform, peri-amygdaloid and lateral entorhinal cortex (see above. Outputs of MOB). This projection terminates in the superficial half of layer I, layer la. Both mitral and tufted cells project to the rostral parts of AON and piriform cortex while the projection to more caudal parts of olfactory cortex becomes progressively dominated by mitral cells (Schoenfeld and Macrides, 1984). 

Piriform cortex, lateral entorhinal cortex and the transitional cortical areas project heavily back to the olfactory bulb (Figs. 13,14, 18,19). The projections are heavier from the rostral than the caudal parts of primary olfactory cortex in rat and mouse (Shipley and Adamek, 1984). A few cells in the posterolateral and medial cortical amygdaloid areas may project to the MOB (Shipley and Adamek, 1984). These feedback projections to the olfactory bulb arise mainly from pyramidal neurons in layers II and III in primary olfactory cortex. 

The transmitter(s) of these olfactory cortical projections to the bulb are not known although glutamate is suspected because that excitatory amino acid is found in many cells in layers II and III of piriform and entorhinal cortex (Kaneko and Mizuno, 1988) (Table 4). These feedback projections from olfactory cortex to the olfactory bulb are believed to primarily excite the GABAergic granule cells in MOB which in turn inhibit firing of mitral cells (Nicoll, 1971) via dendrodendritic synapses between granule and mitral cell dendrites (Halasz and Shepherd, 1983). 

In addition to the feedback projections to the olfactory bulb, olfactory cortex has other extensive connections which can be discussed as four classes intrinsic or local - short connections between neurons in different layers of POC associative - connections with different parts of POC, extrinsic - connections with other structures, and modulatory inputs - afferents that terminate in POC as part of a broader innervation of other cortical and subcortical neural systems. 

Two classes of POC outputs were discussed above the feedback projection back to the olfactory bulb and the association connections between rostral and caudal olfactory cortex. A third class of outputs is treated separately because it represents the projections of POC to brain regions not generally included in the olfactory system per se although their receipt of inputs from POC obviously implicates these POC targets in olfactory function. The extrinsic outputs of POC are both to cortical and subcortical structures (Fig. 19). 

Many brain areas are innervated by neurons projecting from both the locus coeruleus and the lateral tegmental system but there are exceptions (Fig. 8.3). The frontal cortex, hippocampus and olfactory bulb seem to be innervated entirely by neurons with cell bodies in the locus coeruleus whereas most hypothalamic nuclei are innervated almost exclusively by neurons projecting from the lateral tegmental system. The paraventricular nucleus (and possibly the suprachiasmatic nucleus, also) is an exception and receives an innervation from both systems. 

Fig. 2.19 Central pathways and nuclei, (a) Frog AOS Pl/Pm = lateral and medial pallium EP = post, olfactory eminence and nSm = medial Septal nucleus (from Kratskin, 1995). Reptiles and mammals-—afferent pathways from AOB to amygdala nuclei (Cortical C3 and Medial M), with tertiary connections to other central nuclei in hypothalamus (MPOA, VMH and PMN) (from Johnston, 2000). (b) Snake AOS Second-order projection of accessory fibres nAOT - nucleus of AOT AM = anterior amygdala and nSph = nucleus Sphericus. (c) Mammal AOS Projection sites of vomeronasal fibres in cortex and hypothalamus (from Johnston, 1998).

O Virtually all abused substances appear to activate the same brain reward pathway. Key components of the reward pathway are the dopamine (DA) mesocorticolimbic system that projects from the ventral tegmental area (VTA) and the nucleus accumbens (NA) to the prefrontal cortex, the amygdala, and the olfactory tubercle (Figs. 33-3 and 33-4).5 Animal studies... 

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