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PubMed1983

The principal projection pathway between the olfactory bulb and the prepyriform cortex in the cat.

The anatomy and neuroelectric properties of the lateral olfactory tract (LOT) were investigated in the cat. Electron micrographs were obtained from sampled areas across the rostro-caudal projection of the pathway. Fiber diameters were estimated and axon spectra were obtained from three regions corresponding to peduncle, mid-LOT, and caudal-LOT. The mean inside diameter for all measured axons was 1.13 +/- 0.53 microns. The greatest number was found in the peduncle (approximately 600,000 axons). Mid-LOT and caudal-LOT each contained approximately 250,000 axons. Unmyelinated processes were estimated to be more numerous than the myelinated axons. Synaptic structures were also observed in the LOT. Cross-sectional area measurements of the LOT were obtained from tissue prepared for light microscopy. The area decreased from about 0.3 to 0.2 mm2 across the projection from olfactory bulb to cortex. The anatomical data were used to predict the conduction properties of transmission over the LOT. The olfactory bulb mitral cells were stimulated electrically and conduction velocity and temporal dispersion were evaluated in the tract. The strength-duration and stimulus-response curves and the potential profile during stimulation were also obtained. The time constant for LOT axons was 0.3 msec. The stimulus-response curve was sigmoidal in shape for both presynaptic and postsynaptic responses. The relationship between input (the action potentials) and output (cortical postsynaptic potentials) was linear up to 90 times threshold. Action potentials were conducted at 20 m/sec across the pathway over the peduncle and decreased to about 10 m/sec in caudal aspects. The potential profile for action potentials decayed exponentially into the depths of the cortex whereas the synaptic potential was a surface negative dipole field. The axon spectra were convolved with the electrophysiological properties of the LOT to mathematically reconstruct action potentials. The empirically derived mono- and biphasic curves fitted reasonably well with experimentally derived data under various stimulus conditions.

Action Potentials↗
PubMed1977

Dihydroxyphenylacetic acid conjugate: natural occurrence and demonstration of probenecid-induced accumulation in rat striatum, olfactory tubercles and frontal cortex.

Methods for the synthesis of 14C-dihydroxyphenylacetic acid (DOPAC) conjugate and for the fluorometric determination of both free and conjugated DOPAC in the same tissue sample are described. Both free and conjugated DOPAC were demonstrated to occur endogenously in the rat corpus striatum, olfactoy tubercles and frontal cortical area, and the ratio of conjugated DOPAC to free DOPAC was 2-3 times greater in the olfactory tubercles and frontal cortical area than in the striatum. Probenecid administration (200 mg/kg, i.p., 4 and 2h before sacrificing) significantly increased the levels of DOPAC conjugate in all 3 brain areas studied. The levels of free DOPAC were also increased in the olfactory tubercles and frontal cortex by the probenecid treatment, but this increase was much less than that seen for DOPAC conjugate in these regions. Free DOPAC levels in the striatum were unaffected by the probenecid treatment. In all 3 brain areas studied, therefore, probenecid treatment resulted in a significant accumulation of conjugated DOPAC relative to free DOPAC. The magnitude of this effect varied, and was most marked in the frontal cortex. These results suggest that, in order for DOPAC to be transported from the central nervous system via a probenecid-sensitive transport system, it must first be conjugated. Additionally, it appears that the rates of synthesis, metabolism, and transport for both free and conjugated DOPAC may vary greatly among different dopamine-containing brain regions.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Effects of melanostatine (MIF-1) on focal potentials in slices of rat brain cortex.

The effects of tripeptide melanostatine (Melano-Inhibitory Factor--MIF-1) in concentrations 10(-7)-10(-5) M on parameters of focal potentials (FPs) were studied in slices of rat olfactory and parietal cortex. The addition of MIF-1 to perfusion fluid caused in olfactory cortex the primary depression of FP amplitudes evoked by stimulation of the lateral olfactory tract (LOT); this depression was replaced by restoration and prolonged (30-40 min) enhancement of FP amplitudes and by appearance of additional FP components, such as disynaptic EPSPs and IPSPs. In parietal cortex slices MIF-1 caused the elevation of FP amplitudes evoked by stimulating adjoining points. The repetitive perfusion of slices with MIF-1 potentiated the peptide effect on the increase of FP amplitudes. During excitatory period MIF-1 influenced specifically the functional plasticity in olfactory cortex, having facilitated the induction and sustaining of post-tetanic potentiation (PTP). Data observed support the idea of the activatory influence of MIF-1 on the CNS at the cellular level, which is likely to lie in the ground of antidepressant properties of this peptide.

Animals↗
PubMed1995

Localization and functional coupling of HGF and c-Met/HGF receptor in rat brain: implication as neurotrophic factor.

Hepatocyte growth factor (HGF), a natural ligand for the c-met protooncogene product, has mitogenic, motogenic and morphogenic activities for various cell types and functions as a organotrophic factor for regeneration of the liver, kidney and lung. We obtained evidence that HGF may function as a novel neurotrophic factor in the central nervous system. Northern blot analysis showed that 6 kb HGF mRNA and 9 kb c-Met/HGF receptor mRNA are expressed in various regions of the adult rat brain. In situ hybridization analysis revealed that intense hybridization signals for HGF mRNA were localized in cerebral cortex, hippocampus and amygdala. Consistently, specific localization of HGF protein in neurons of these regions was detected by immunohistochemical analysis and non-neuronal glial cells in cingulum, cerebellum, pons and medulla were also specifically stained. Specific intense hybridization signals for c-Met/HGF receptor mRNA were also widely distributed in the brain, including neurons of olfactory bulb, cerebral cortex, primary olfactory cortex, hippocampus and cerebellum. On the basis of the co-expression of HGF and c-Met/HGF receptor in hippocampal neurons, we found that HGF prolonged survival of embryonic hippocampal neurons in primary culture: HGF elicited maximal surviving effect at 0.5-1 ng/ml and the potency was comparable to that of nerve growth factor. More importantly, expression of both HGF and c-Met/HGF receptor mRNAs was markedly induced in response to cerebral ischemic injury. We propose that HGF functions as a neurotrophic factor in the central nervous system and that this neurotrophic function may have a role in the survival and reconstruction of specific neurons in response to cerebral injury.

Animals↗
PubMed1980

A transthalamic olfactory pathway to orbitofrontal cortex in the monkey.

1. Evoked potentials restricted to the magnocellular portion of the mediodorsal nucleus (MDmc) of the thalamus were recorded after stimulation of the olfactory bulb (OB) and the posterior orbital cortex of the frontal lobe (OFC). Potentials evoked by stimulation of OB were probably trans-synaptically elicited, while potentials evoked by stimulation of OFC were probably a result of antidromic activation. 2. The area in which stimulation could elicit antidromic evoked potentials in MDmc was located in the centroposterior portion of OFC (CPOF). This area corresponds approximately to Walker's (80) area 13 and to von Bonin and Bailey's (9) area FF, and is situated medial and just anterior to a previously identified olfactory area, the lateroposterior portion of OFC (LPOF), which receives olfactory impulses through the hypothalamus. 3. Using extracellular microelectrodes, 58 neurons that responded with short latencies to OFC stimulation were identified in MDmc. To determine whether these neurons were activated antidromically by CPOF stimulation, three conventional neurophysiological criteria were applied; 20 of 58 neurons satisfied all the three criteria. Hence, they were concluded to be thalamocortical relay (TCR) neurons. 4. Intracellular recording of MDmc neurons disclosed that CPOF stimulation elicits an antidromic spike potential accompanied by an afterhyperpolarization. This hyperpolarization was presumed to be due to concurrent stimulation of inhibitory orbitothalamic fibers. It was also shown that EPSP-like depolarizations with superimposed spike potentials often occurred in the middle of the afterhyperpolarization. 5. Intracellular recording of MDmc neurons strongly suggested that the remaining 38 neurons that did not satisfy one of the three criteria were also TCR neurons. 6. These studies provide electrophysiological evidence for a transthalamic olfactory pathway from OB through MDmc to CPOF. 7. Using an extracellular recording technique, responses of neurons to eight odors were examined in CPOF and MDmc of unanesthetized awake monkeys. When these results were compared with the responses of neurons to the same odors in OB, prepyriform-amygdaloid area, and LPOF, it was concluded that the newly found transthalamic olfactory pathway to CPOF is very different in function from the previously demonstrated transhypothalamic olfactory pathway to LPOF.

Animals↗
PubMed1991

Kindling-induced potentiation in the piriform cortex.

At intensities sufficient to induce epileptiform afterdischarges, repeated electrical stimulation of limbic structures can lead to the development of permanent increases in the strength of the epileptiform response (kindling). Field potentials evoked by pulse stimulation are also increased in amplitude in a number of forebrain pathways following kindling. This kindling-induced potentiation effect is similar in many respects to the 'long-term potentiation' (LTP) effect which is produced by non-epileptogenic stimulation. There are, however, some interesting differences. For example, kindling-induced potentiation can far outlast LTP. In these experiments, we attempted to determine the longevity of the kindling-induced potentiation of the response evoked in the piriform cortex by olfactory bulb stimulation, following olfactory bulb kindling. This system was targeted because both the olfactory bulb and the piriform cortex are highly reactive kindling sites. In addition, we used the paired pulse technique to monitor facilitation and inhibition in this system. Kindling was found to induce a potentiation in the piriform field potential that lasted for at least 3 months (the period of the experiment) with little or no decay. Kindling also produced a decrease in paired pulse facilitation. In some animals the net facilitation was changed to a net depression. These results are consistent with the interpretation that kindling produces an increase in recurrent inhibition in the piriform cortex. The paired pulse measures, however, returned to near baseline levels over the 3-month test period.

Animals↗
PubMed2004

Crossmodal integration--insights from the chemical senses.

Our understanding of the neural correlates of crossmodal binding in the human brain derives almost exclusively from studies of audition, vision and somatosensation. A new study by Gottfried and Dolan extends our understanding of multisensory integration by showing that facilitation of odor detection by visual cues depends on object congruency, as well as on enhanced activity in the superior temporal sulcus and a region of the orbitofrontal cortex that is adjacent to olfactory association cortex.

Brain Mapping↗
PubMed1980

[Comparative volumetric analysis of the principal subdivisions of the telencephalon in saurian reptiles].

The volumetric measure of the main subdivisions of the telencephalon has been carried on 24 species of Lizards and 2 species of Snakes. The studied structures are termed as follows: main and accessory olfactory bulbs, medial cortex (M 1 and M 2), dorsal cortex (D 1, D 2 and D 3), lateral cortex (L), Septum, Tuberculum olfactorium, dorsal and ventral striatum, amygdala and nucleus sphaericus. The analysis of the datas makes use of the SNEL L's formula which relates the volume of the various telencephalic subdivisions (V) to the somatic weight (S): V = k x S alpha. Each alpha value is compared to the value of the coefficient of allometry (A) of the whole brain. The evolutive (phylogenetic) growth of a structure is said fast (or slow) when its corresponding alpha value is higher (or lower) than the encephalic A value. At the cortical level such analysis shows the progressive nature of the dorsal cortex. A partition of the sample into Lacertomorpha (14 species) and Dracomorpha (10 species) (in agreement with the NORTHCUTT'S definition of his Type I and Type II Lizards) corroborates this cortical detail, more distinctly with the second group as well (especially for the D 2 portion). Moreover the high number of progressive structures among the Dracomorpha leads to consider this group as phylogenetically the most advanced in the Order of Lizards. The somatic indices are calculated according the allometric characteristics of the Reference Lizards. The judicious choice of some species allows to show how the development of a biological function may be expressed by the values of the indices of the related structures. For examples: dorsal cortex, dorsal striatum and mode of locomotion; olfactory bulbs, lateral cortex, part M 1 of the medial cortex and olfactory system; D 3 subdivision of the dorsal cortex and visual performances. The duality between Lacertomorpha and Dracomorpha is therefore corroborated by significant differences found for the various indices of a great number of telencephalic subdivisions. It leads moreover to find, grosso modo, two functional types of Lizards: moving-on-the-ground and wellsmelling (mainly Lacertomorpha) on the one hand, arboreal and with a fine vision (mainly Dracomorpha) on the other hand. The isoponderal percentages take an useful illustration of these results; it allows to establish the telencephalic pattern of a standard Lizard in which the pallium keeps the larger part (42%); in the pallium itself, the M 1 subdivision of the medial cortex has the most important percentage, a little more than the D 2 part of the dorsal cortex. A comparative study carried on 2 Snakes gives for Boa constrictor the lowest values of the indices, for almost all the structures. In return Natrix natrix stays, for a great number of structures, close to the level of the legless Lizards; this last result confirms distinctly the two levels of telencephalization already found in Snakes (PLATEL, 1976 a).

Amygdala↗
PubMed1998

Habituation of odor responses in the rat anterior piriform cortex.

Simultaneous recordings of main olfactory bulb (MOB) and anterior piriform cortex (aPCX) neuron responses to repeated and prolonged odor pulses were examined in freely breathing, urethan-anesthetized rats. Comparisons of odor responses were made between multi-unit recordings of MOB activity and single-unit extracellular and intracellular recordings of Layer II/III aPCX neurons. Odor stimuli consisted of either 2-s pulses repeated at 30-s intervals or a single, prolonged 50-s stimulus. Respiration rate was monitored throughout. MOB and aPCX neuron responses to odor were quantified both through firing frequency and through the temporal patterning of firing over the respiratory cycle. The results demonstrate that aPCX neurons habituate significantly more (faster) than MOB neurons with both repeated and prolonged stimulation paradigms. This enhanced habituation is expressed as both a decrease in aPCX firing despite maintained odor-evoked MOB input and as a decrease in aPCX respiratory cycle entrainment despite maintained MOB cyclic input. Intracellular aPCX recordings suggest that several mechanisms may be involved in this experience-induced change in aPCX function, including 1) decreased excitatory driveof aPCX neurons, 2) decreased excitability of aPCX neurons,and/or 3) enhancement in odor-evoked inhibition of aPCX neurons. These studies provide the initial basis for understanding the mechanisms of nonassociative plasticity in olfactory cortex.

Analysis of Variance↗
PubMed1994

N-acetylaspartate and N-acetylaspartylglutamate levels in Alzheimer's disease post-mortem brain tissue.

The tissue concentrations of two related amino acid derivatives, N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) were determined in autopsy hippocampus, amygdala, cerebellar cortex and olfactory bulb of Alzheimer's disease patients and age-matched non-demented controls, using reverse-phase HPLC and fluorescence detection after precolumn derivatisation with the fluorophore 2-aminoanthracene. In Alzheimer's disease, NAA and NAAG concentrations were significantly reduced in the hippocampus (by 38 and 24%) and the amygdala (by 28 and 22%), but not in the olfactory bulb and the cerebellar cortex. These results indicate that the concentrations of NAA and NAAG are selectively decreased in brain areas affected by pathology in Alzheimer's disease.

Aged↗
PubMed2000

Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex.

When a food is eaten to satiety, its reward value decreases. This decrease is usually greater for the food eaten to satiety than for other foods, an effect termed sensory-specific satiety. In an fMRI investigation it was shown that for a region of the orbitofrontal cortex the activation produced by the odour of the food eaten to satiety decreased, whereas there was no similar decrease for the odour of a food not eaten in the meal. This effect was shown both by a voxel-wise SPM contrast (p <0.05 corrected) and an ANOVA performed on the mean percentage change in BOLD signal in the identified clusters of voxels (p <0.006). These results show that activation of a region of the human orbitofrontal cortex is related to olfactory sensory-specific satiety.

Eating↗
PubMed1999

Potentiation of late components in olfactory bulb and piriform cortex requires activation of cortical association fibers.

Previous research has demonstrated that repeated high-frequency stimulation of the granule cell layer of the olfactory bulb (OB) produces an enduring potentiation of late components (PLC) in potentials evoked in the OB and piriform cortex (PC), while leaving the monosynaptic EPSP produced by OB mitral cells in PC pyramidal cells unaltered. Two experiments were conducted using male Long-Evans rats with chronically implanted electrodes to assess the relative contribution to this potentiation of the two main fiber systems that interconnect the OB and PC: the lateral olfactory tract (LOT), which contains mitral cell axons that synapse on PC pyramidal cells, and the PC association fiber system, which consists of the axons of PC pyramidal cells that synapse on several cell populations within the PC and on granule cells in the OB. The results indicate that stimulation of PC association fibers is both necessary and sufficient to duplicate the pattern of potentiation seen following OB stimulation in previous experiments. LOT stimulation had no consistent effect, and coactivation of the LOT and PC association fibers was no more effective than activation of PC association fibers alone. Possible mechanisms underlying this effect are discussed, including (1) long-term potentiation (LTP) at synapses made by the axons of PC pyramidal cells on neurons in the OB and PC; and (2) repetitive firing in PC pyramidal cells due to regenerative excitation in a population of deep cells in the PC and endopiriform nucleus.

Animals↗
PubMed2001

Olfactory learning is associated with increased spine density along apical dendrites of pyramidal neurons in the rat piriform cortex.

We studied the effect of olfactory learning on the dendritic spine density of pyramidal neurons in the rat piriform (olfactory) cortex. Rats were trained to distinguish between two pairs of odours in an olfactory discrimination task. Three days after training completion, rats were killed and layer II pyramidal neurons identified by Golgi impregnation were examined with a light microscope. Counts of visible spines were performed along the secondary and tertiary branches of both the apical dendrites and the basal dendrites, which are the sites of intracortical synaptic inputs. An estimate of the true spine density was obtained using Feldman and Peters' method (1979, The Journal of Comparative Neurology, 188, 527--542). The estimated true spine density along apical dendrites was higher in neurons from trained rats than those in pseudotrained and naive rats by 15%. As length of spiny dendrites did not change significantly after learning, the learning-related increase in spine density in neurons from trained rats may indicate on an increased number of excitatory synapses interconnecting pyramidal neurons in the piriform cortex, following olfactory learning.

Animals↗
PubMed1994

Recovery of olfactory behavior. I. Recovery after a complete olfactory bulb lesion correlates with patterns of olfactory nerve penetration.

The olfactory system is an excellent system in which to study issues related to potential functional recovery after a debilitating brain injury. The olfactory system is well-characterized, easily accessible and there are a vast number of studies available from a variety of perspectives. The experimental aim of this research is to examine the anatomical correlates associated with potential behavioral recovery in rats that receive complete olfactory bulb lesions as neonates or as adults. The results show that behavioral recovery occurs only when olfactory nerve penetration of the central nervous system is observed. Further, both olfactory nerve penetration and behavioral recovery are age-dependent phenomena. The olfactory nerve penetration only occurs when the olfactory bulb lesion is performed in neonates. Behavioral recovery of olfactory ability follows a linear trend and reaches near normal levels during the six weeks behavioral testing period. Histological analysis using an antibody for olfactory marker protein (an olfactory nerve-specific marker) reveals two potential candidates for the anatomical pathway responsible for behavioral recovery: olfactory nerve to orbital frontal cortex and olfactory nerve to olfactory peduncle. This report presents evidence that recovery of olfactory ability can occur in the absence of the olfactory bulb if the lesion is performed when the rat is still a neonate.

Animals↗