Ventrostriopallidal functional interconnections with cortical and quasi-cortical regions.

A total of 287 neurons were antidromically driven in quasi-cortical regions, i.e., anterior olfactory nucleus (24%), basolateral amygdala (13%), main olfactory bulb (4%), prefrontal cortex (37%), and in the hippocampal formation (22%) following macro- and microstimulation of the rat's ventrostriopallidal region (VSPR). In addition, a substantial number of units (n = 175) were also transynaptically affected in all these structures by shocks delivered to the VSPR. Excitatory effects were detected in 50 neurons (56.1% of responsive cells), 36 cells (40.4%) responding with inhibition of spontaneous discharges. Conversely, stimulation of cortical and quasi-cortical regions antidromically discharged (n = 37) or transynaptically affected (n = 151) units in the VSPR; 168 neurons were not responsive to VSPR stimulation. Axon collateralization (branching) of 14 neurons in anterior olfactory nucleus, basolateral amygdala, and hippocampal formation was revealed with the use of the reciprocal collision test. Conduction properties of 35 neurons, evaluated by paired-pulse stimulation, indicated that only 26% showed a significant increase in conduction velocity and a decrease in threshold during the supernormal phase. The present findings confirm and extend previous neuroanatomical studies that have, first, described strong interconnections between the neocortex and striatal structures, and second, that the VSPR as suggested by previous structural, hodological, and histochemical studies, seems to maintain a more close relationship with olfactory related structures than hitherto suspected.

Cortical and quasi-cortical regions innervate ventrostriopallidal structures in the rat: an electrophysiological analysis.

Antidromic unit driving was utilized to demonstrate afferent projections from prefrontal cortical (PFC) and quasi-cortical structures (main olfactory bulb, MOB; anterior olfactory nucleus, AON; basolateral amygdaloid nucleus, BLA) to the ventrostriopallidal region (VSPR) of the rat. In all regions explored, a substantial number of antidromically invaded neurons were found following electrical stimulation of the VSPR. In addition, both the AON and the amygdalostriatal zone harbor cells with branched axons which innervate the MOB and the VSPR and the agranular insular cortex and the VSPR, respectively. These results support and extend previous neuroanatomical and neurophysiological data on afferent connections of the VSPR and emphasize the fact that several regions of the basal forebrain, which are actively involved in processing of olfactory information, and the VSPR, are more closely interrelated than hitherto suspected.

The olfactory system and Alzheimer's disease.

Alzheimer's disease (AD) is considered to be the number one health problem and seems to be reaching epidemic proportion in the USA. The cause of AD is not known, a reliable animal model of the disease has not been found and appropriate treatment of this dementia is wanting. The present review focuses on the possibility that a virus or exogenous toxic materials may gain access to the CNS using the olfactory mucosa as a portal of entry. Anterograde and retrograde transport of the virus/zeolites to olfactory forebrain regions, which receive primary and secondary projections from the main olfactory bulb (MOB) and which, in turn, project centrifugal axons to the MOB, may initiate cell degeneration at such loci. Pathological changes may, thus, be initially confined to projecting and intrinsic neurons localized in cortical and subcortical olfactory structures; arguments are advanced which favor the view that excitotoxic phenomena could be mainly responsible for the overall degenerative picture. Neurotoxic activity may follow infection by the virus itself, be facilitated by loss of GABAergic terminals in olfactory cortex, develop following repeated episodes of physiological long term potentiation (which unmasks NMDA receptors) or be due to excessive release, faculty re-uptake or altered glutamate receptor sensitivity. Furthermore, a reduction in central inhibitory inputs to the MOB might then result in disinhibition of mitral/tufted neurons and enhance the excitotoxic phenomena in the MOB projecting field. Within this context, and in line with recent studies, it is believed that pathology begins at cortical (mainly olfactory) regions, basal forebrain neurons being secondarily affected due to retrograde degeneration. In addition, failure to produce a critical level of neurotrophic factors by a damaged MOB and olfactory cortex, could adversely affect survival of basal cholinergic neurons which innervate both regions. Support for these hypothesis is provided, first, by recent reports on pathological findings in AD brains which seem to involve preferentially the olfactory and entorhinal cortices, the olfactory amygdala and the hippocampus, all of which receive primary or secondary projections from the MOB; secondly, by the presence of severe olfactory deficits in the early stages of the disease, mainly of a discriminatory nature, which points to a malfunction of central olfactory structures.

Electrophysiological connections of neurons in ventral pallidal regions of the olfactory tubercle with the main olfactory bulb and piriform cortex.

Field potential and single unit recordings were used to assess the connections of the olfactory tubercle (OT) with the main olfactory bulb (MOB) and the piriform cortex (PC) in urethane-anesthetized rats. Current generators of depth profiles evoked in OT following MOB stimulation were localized 300 microns superficial to those elicited by PC shocks, suggesting that afferents from the MOB and PC end in different regions of the OT. Following MOB and PC stimulation antidromically invaded neurons were recorded in the ventral pallidal regions of the OT and in the vicinity of the islands of Calleja, respectively. These results demonstrate that the OT, which receives a monosynaptic input from the MOB, projects back to the bulb and that the PC seems to be also reciprocally linked with differentiated structures in the OT.

Current generators and properties of late components evoked in rat olfactory cortex.

Following main olfactory bulb (MOB) stimulation at frequencies of 0.1-0.3 Hz, in addition to early field potentials, a frequency-sensitive, surface negative late N2 wave (latency range: 63-96 msec) followed occasionally by a late N3 transient, was evoked in the piriform cortex and endopiriform nucleus of the rat. The N2 wave inverted polarity at the Ib-II cortical layer interface (P2 wave) and was associated with late unit discharges 200 to 1200 microns deep to the turnover point. Response probability, peak latency, recovery curve and frequency-sensitivity of the P2 wave were not significantly different in animals under urethane or pentobarbital. Current-source-density (CSD) analysis revealed that the N2 wave generators were localized to the Ib-II layer interface. Since inhibitory activity does not contribute substantially to the second derivative curve, CSD analysis strengthens the assumption that late components (LCs) are excitatory events (compound EPSPs) presumably generated on the proximal apical dendritic segments of pyramidal cells by association axons. The early "b" wave in a test response was facilitated, rather than occluded, when a LC was present in the conditioning response, or when the priming volley was delivered to the mediodorsal thalamic nucleus. Clustering of unit and field activity in two distinct periods of the evoked response separated by a prolonged interval of cell silence suggests that cortical coding of olfactory cues might be more efficiently achieved by temporal modulation of the neuronal response rather than by spatial distribution of firing patterns.

A computer program for automatic plotting of isopotential contours in CNS.

A computer program was developed in a Basic (Applesoft) version for generating up to five isopotential curves from field potentials recorded in nervous structures. Voltages are fed according to a cartesian coordinate system, and an area is delineated each four points in which a certain number of intermediate voltage points are calculated, according to the required resolution. The calculated values are compared to those prefixed for each curve and, if similar, their coordinates are stored in corresponding bidimensional matrixes. A special subroutine was designed for constructing an isometric tridimensional perspective of the isopotential curve ensemble. The reliability of this program was tested in the localization of sensory representation areas on the neocortex of the South American armadillo (Chaetophractus vellerosus) studied by evoked potential mapping following visual, auditory and somatosensory stimuli. The isopotential curves traced permitted a quantitative evaluation of the cortical activated areas, and from their topographical distribution, relative unresponsive zones could be inferred where only inconspicuous responses were obtained. It is concluded that the present program provides a reliable and fast method for studying the evoked potential's spatial distribution over the entire neocortex. In addition, it can be extended to the study of curves or contours which connect equivalent values pertaining to biophysical magnitudes other than voltage data.

Reciprocal functional connections of the olfactory bulbs and other olfactory related areas with the prefrontal cortex.

Reciprocal putative connections of the prefrontal cortex (PFC) (agranular insular, ventral and lateral orbital region) with the ipsi and contralateral main olfactory bulb (IOB; COB), the mediodorsal thalamic nucleus (MD), the basolateral amygdaloid nucleus (BLA) and the piriform cortex (PC) were investigated with electrophysiological techniques. Evoked field responses and orthodromic unit driving, generated in PFC following electrical stimulation of the above mentioned structures, were abolished following topical application of KCl, except for COB evoked mass potentials. Thus, locally generated activity was elicited in agranular insular cortex following IOB activation, the same region where recently, the taste cortex in the rat was localized. Since gustatory-visceral afferent information reaches insular cortex via 2-3 synaptic relays, autonomic, olfactory and gustatory inputs may interact at this level, and, as suggested previously for the mouse, play a key integrative role in flavor perception. Antidromically invaded neurons, 47% of which were identified by the collision-extinction technique, were also found in PFC areas which overlapped to a considerable extent with those from which orthodromic unit responses were obtained. In particular, closely spaced neurons in ventrolateral orbital (VLO) and lateral orbital (LO) regions were antidromically invaded following IOB and PC shocks; some neurons antidromically discharged by IOB were also transsynaptically activated following PC stimulation. These findings are in agreement with recent neuroanatomical studies which demonstrate axonal projections from PFC neurons to the IOB and COB in the rat and South American armadillo. In addition, stimulation of PFC regions dorsal to the rhinal fissure mostly inhibited spontaneous unit discharges recorded at the mitral cell layer of the IOB, suggesting that this effect may be partially mediated by excitatory inputs of prefrontal axons onto granule cells. The conduction properties, antidromic thresholds and activity-dependent variations in conduction velocity (CV) of bulbopetal neurons in prefrontal cortex were found to be similar to those exhibited by cells projecting to the IOB from olfactory peduncle regions, but not to those present in bulbopetal neurons of the horizontal limb of diagonal band, indicating that the OB may be subjected to centrifugal control by at least two cell groups differing in both histochemical and electrophysiological properties.

Axonal projections and conduction properties of olfactory peduncle neurons in the armadillo (Chaetophractus vellerosus).

Extracellular unit recording was employed to study the axonal properties and efferent projections of antidromically identified neurons in the olfactory peduncle (OP) region of a primitive eutherian macrosmatic mammal, the south american armadillo (Chaetophractus vellerosus). Of 72 cells which satisfied the criteria for antidromic invasion, 55 (76%) and 17 (24%) responded to ipsi- and contralateral olfactory bulb (IOB; COB) stimulation, respectively. The absolute refractory period (3.25 +/- 0.3 ms; mean +/- SE) and the conduction velocity (CV; 1.94 +/- 0.2 m/s; mean +/- SE) of IOB and COB driven neurons were negatively correlated (r = -0.52; p less than 0.001). In paired-shock tests (8-1950 ms interval), and early supernormal period (SPN) of increased CV and excitability was found following the relative refractory period in 82% of tested cells (N = 50); this period was followed by a late subnormal phase (SBN) of decreased CV and increased threshold in 58% of neurons (N = 50). Significant correlations were found to exist between: CV and absolute magnitude of latency variation (r = -0.55; p less than 0.001; n = 43), CV and duration of SPN and SBN periods (r = -0.60; p less than 0.002; n = 24 and r = 0.58; p less than 0.02; n = 19, respectively) and between duration of SPN and SBN phases (r = 0.79; p less than 0.001; n = 30). Maximum latency variation during the SPN and SBN periods was attained in a gradual, additive manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute prenatal alcohol exposure in rats: a behavioral study.

Pregnant rats were exposed to ethanol (two doses of 6.4 g/kg spaced by an interval of 6 hours, administered through an intragastric cannula) on the 8th day of gestation; control rats received two identical administrations of isocaloric sucrose. No significant differences were found in body weight and litter size of experimental and control pups 24 hours after delivery. When offsprings of ethanol treated mothers were tested in different postnatal behavioral tasks, significant developmental delays (suckling behavior and surface righting) were revealed during the lactation period, and an impaired passive avoidance performance was found at 40 days old compared to control offsprings.

An automatic device for determining threshold variations in antidromically activated neurons.

A device was designed and constructed with the purpose of evaluating threshold variations for antidromic invasion of extracellularly recorded neurons. Identification of a neuron is carried out by two procedures, an amplitude discriminator, which isolates the spike from the baseline noise, and by a latency window which is set accordingly to the neuron's antidromic latency. During threshold evaluation, the duration of an electric pulse applied to the neuron's axon is automatically varied depending on the presence or not of an action potential. For a given spike, the stimulus is progressively decreased (-delta i) up to a point where the neuron ceases to respond and thereafter, the stimulus amplitude is progressively increased (+delta i) until slightly suprathreshold values are obtained. The procedure guarantees a discharge probability of the neuron equivalent to 50% of all applied stimuli, and the simple monitoring of the stimulus amplitude is enough to obtain the threshold value for a predetermined intensity. The reliability of this device was checked in studies related to threshold variations in neurons antidromically driven in prefrontal cortex following stimulation of the ipsi and contralateral olfactory bulb. Variations in excitability were found during and following tetanic stimulation and throughout the axon's supernormal conduction period. This technique allows the assessment of threshold variations in antidromic driving, not only in the present experimental design, but also in other conditions induced by changes in extracellular ionic concentrations, drug applications or in those produced by excitatory or inhibitory synaptic activity on the neuron under study.

Current generators and properties of early components evoked in rat olfactory cortex.

Depth-profile, current-source-density (CSD) and impedance analysis were used to determine the current generators of secondary waves "a" and "b" in the response evoked in pyriform cortex (PC) of the urethane anesthetized rat following OB or LOT stimulation. Positive peaks (sinks) in the second-derivative curves of the "a" and "b" waves were localized at 50-75 and 225-250 microns deep, respectively. Cortical impedance was significantly (p less than 0.01) correlated with the cell packing density of PC layers, being maximal close to the zero dipole point of the gross evoked response; magnitude of conductivity gradients was, however, insufficient to alter the interpretation of positive and negative peaks in terms of net membrane currents. Post-tetanic and/or frequency potentiation of PC responses but not long-term potentiation were found in the majority of animals tested. Recovery of the test "b" wave was faster when using paired-shock stimulation at 3.0 Hz than at 0.3 Hz; suppression of this component following a conditioning OB volley could be overcome and the "b" wave facilitated if either a long-latency component (i.e., 65-100 msec) was present in the priming response, or if the conditioning stimulus was delivered to the mediodorsal thalamic nucleus (MDT). These results confirm and extend similar ones in other species, suggesting that following OB or LOT stimulation three successive excitatory processes take place in PC neural elements of the rat under urethane anesthesia: an initial monosynaptic excitation of distal segments of apical dendrites of layer II cells, and to a lesser extent, also of layer III neurons ("a" wave), followed by action potentials in their respective somas (PS wave); subsequently, long association axons give rise to a di or polysynaptic compound EPSP in proximal apical and possibly also, in basal pyramidal dendrites ("b" wave; early reactivation process). Finally, a "late" reactivation takes place in PC involving neurons which participated in the early reactivation process (late component). In addition, heterosynaptic facilitation of the "b" wave in the PC evoked response follows MDT conditioning stimulation.

Origin and plastic properties of late components evoked in the rat's but not in the armadillo's prepyriform cortex.

Following ipsilateral olfactory bulb (IOB) stimulation long-latency (62-89 ms) gross and unit responses were evoked in the prepyriform cortex of rats prepared under urethane or pentobarbital, but were absent in 23 armadillos explored under the same anesthetics. Depth profile and current source density analysis revealed that generators of early and late components (LC) lie within cortical layers Ia-Ib, suggesting that LC may represent a compound depolarizing excitatory postsynaptic potential, generated by recurrent excitation of pyramidal cells. LC satisfied, in addition, several parametric requirements for habituation, favoring the hypothesis that late response waning following a period of predictable, repetitive and invariant stimulation, might be related to behavioral habituation to odors.

Olfactory connections of substantia innominata and nucleus of the horizontal limb of the diagonal band in the rat: an electrophysiological study.

Extracellular unit recordings performed on 113 spontaneously discharging neurons in the substantia innominata-nucleus of the horizontal limb of the diagonal band region revealed that 46 (41%) were transsynaptically discharged or inhibited following stimulation of the main and accessory olfactory bulb (MOB, AOB) and the prepyriform cortex (PPC). A significantly greater number of cells were responsive to MOB and PPC than to AOB shocks. Eight (7%) neurons were antidromically invaded following MOB volleys. These findings suggest that the MOB has functional reciprocal connections with the 'ventral striatum', a region which can function, presumably as a nodal point for convergence of visual, gustatory and olfactory information relevant to feeding and drinking behavior.

Sensory control of the hypothalamus and the neuroendocrine system.

A study was made of the control of the hypothalamus and neuroendocrine complex by the specialized receptors: the eye, the ear and the olfactory complex. The ancient and modern evidence that light, acting on the optic system, can influence hypothalamic, hypophyseal, endocrine reactions was reviewed and the recently acquired evidence that an optic-hypothalamic-autonomic-pineal-hypothalamic circuit exists which controls liberation of "releasing hormones". Evidence was presented to show that the ear and eye, extero-and interoceptive influences affect lactation and oxytocin secretion by action through the hypothalamus. It was also shown that electrochemical stimulation of the olfactory bulbs can affect both sexual behavior and gonadotropin secretion. Finally, it was shown that the olfactory system exerts some control over water intake, sodium appetite and antidiuretic hormone secretion. Progress in a long term cooperative study of the role of exteroceptor control of neuroendocrine functions was reported.