Receptive fields in the rat piriform cortex.

Current models of odor discrimination in mammals involve molecular feature detection by a large family of diverse olfactory receptors, refinement of molecular feature extraction through precise projections of olfactory receptor neurons to the olfactory bulb to form an odor-specific spatial map of molecular features across glomerular layer, and synthesis of these features into odor objects within the piriform cortex. This review describes our recent work on odor and spatial receptive fields within the anterior piriform cortex and compares these fields with receptive fields of their primary afferent, olfactory bulb mitral/tufted cells. The results suggest that receptive fields in the piriform cortex are ensemble in nature, highly dynamic, and may contribute to odor discrimination and odor memory.     

Acetylcholine and associative memory in the piriform cortex

The significance of cholinergic modulation for associative memory performance in the piriform cortex was examined in a study combining cellular neurophysiology in brain slices with realistic biophysical network simulations. Three different physiological effects of acetylcholine were identified at the single-cell level: suppression of neuronal adaptation, suppression of synaptic transmission in the intrinsic fibers layer, and activity-dependent increase in synaptic strength. Biophysical simulations show how these three effects are joined together to enhance learning and recall performance of the cortical network. Furthermore, our data suggest that activity-dependent synaptic decay during learning is a crucial factor in determining learning capability of the cortical network. Accordingly, it is predicted that acetylcholine should also enhance long-term depression in the piriform cortex.     

N-methyl-d-aspartate andl-aspartate activate distinct receptors in piriform cortex

The effects of ionophoretically applied N-methyl-DL-aspartate (NMDA) and aspartate on identified pyramidal neurons in rat piriform cortex were examined in isolated, submerged, and perfused brain slices. NMDA was more potent than aspartate in eliciting neuronal discharge. Perfusion of the acidic amino acid antagonists, DL-2-amino-5-phosphonovalerate (APV), 10(-6) or 10(-5) M, DL-2-amino-7-phosphonoheptanoate (APH), 10(-5) M, and gamma-D-glutamylglycine (gamma DGG), 10(-5) M, selectively blocked the response to NMDA without effect on the response to aspartate. At higher concentrations which blocked responses to both NMDA and aspartate, gamma DGG blocked kainate responses and depressed glutamate and quisqualate responses. These results suggest that in piriform neurons NMDA and aspartate act at distinct receptor sites, not a common receptor site, and that both of these sites are distinct from those that mediate responses to glutamate, quisqualate, and kainate.     

Long-term potentiation in the piriform cortex is blocked by lead

Summary 1. Long-term potentiation (LTP) is a prolonged increase in synaptic efficacy that is triggered by a brief tetanic stimulation at certain central synapses. LTP is one of the best available model systems available to the neurophysiologist of neuronal plasticity such as that underlying learning and memory.2. We have studied the susceptibility of LTP to blockade by lead as a test of the hypothesis that the negative effect of lead on intelligence in children may result from interference with this process. LTP was studied in slices of rat piriform cortex. At this site, as in many other central synapses, LTP requires activation of postsynapticN-methyl-d-aspartate (NMDA) receptors, and we investigated whether lead actions, if any, were mediated via effects on NMDA-activation ion channels or, alternatively, at voltage-activated calcium channels.3. We find that lead blocks LTP at low micromolar concentrations. However, concentrations of lead that totally block LTP had no apparent effect on either NMDA-activated responses or presynaptic calcium channels, as monitored by transmitter release from presynaptic terminals.4. While the mechanism of lead blockade of LTP remains to be determined, these observations are consistent with the hypothesis that the cognitive effects of lead neurotoxicity may result from effects on LTP.     

Recurrent circuitry dynamically shapes the activation of piriform cortex

In the piriform cortex, individual odorants activate a unique ensemble of neurons that are distributed without discernable spatial order. Piriform neurons receive convergent excitatory inputs from random collections of olfactory bulb glomeruli. Pyramidal cells also make extensive recurrent connections with other excitatory and inhibitory neurons. We introduced channelrhodopsin into the piriform cortex to characterize these intrinsic circuits and to examine their contribution to activity driven by afferent bulbar inputs. We demonstrated that individual pyramidal cells are sparsely interconnected by thousands of excitatory synaptic connections that extend, largely undiminished, across the piriform cortex, forming a large excitatory network that can dominate the bulbar input. Pyramidal cells also activate inhibitory interneurons that mediate strong, local feedback inhibition that scales with excitation. This recurrent network can enhance or suppress bulbar input, depending on whether the input arrives before or after the cortex is activated. This circuitry may shape the ensembles of piriform cells that encode odorant identity.     

Neuromodulation and the functional dynamics of piriform cortex.

Acetylcholine and norepinephrine have a number of effects at the cellular level in the piriform cortex. Acetylcholine causes a depolarization of the membrane potential of pyramidal cells and interneurons, and suppresses the action potential frequency accommodation of pyramidal cells. Acetylcholine also has strong effects on synaptic transmission, suppressing both excitatory and inhibitory synaptic transmission. At the same time as it suppresses synaptic transmission, acetylcholine enhances synaptic modification, as demonstrated by experiments showing enhancement of long-term potentiation. Norepinephrine has similar effects. In this review, we discuss some of these different cellular effects and provide functional proposals for these individual effects in the context of the putative associative memory function of this structure.     

Olfactory predictive codes and stimulus templates in piriform cortex

Neuroscientific models of sensory perception suggest that the brain utilizes predictive codes in advance of a stimulus encounter, enabling organisms to infer forthcoming sensory events. However, it is poorly understood how such mechanisms are implemented in the olfactory system. Combining high-resolution functional magnetic resonance imaging with multivariate (pattern-based) analyses, we examined the spatiotemporal evolution of odor perception in the human brain during an olfactory search task. Ensemble activity patterns in anterior piriform cortex (APC) and orbitofrontal cortex (OFC) reflected the attended odor target both before and after stimulus onset. In contrast, prestimulus ensemble representations of the odor target in posterior piriform cortex (PPC) gave way to poststimulus representations of the odor itself. Critically, the robustness of target-related patterns in PPC predicted subsequent behavioral performance. Our findings directly show that the brain generates predictive templates or "search images" in PPC, with physical correspondence to odor-specific pattern representations, to augment olfactory perception.     

Long-term modifications in the strength of excitatory associative inputs in the piriform cortex

Afferent olfactory information, in vivo and in vitro, can be rapidly adapted to through a metabotropic glutamate receptor (mGluR)-mediated attenuation of synaptic strength. Specific cellular and synaptic mechanisms underlying olfactory learning and habituation at the cortical level remain unclear. Through whole-cell recording, excitatory postsynaptic currents (EPSCs) were obtained from piriform cortex (PC) principal cells. Using a coincidental, pre- and postsynaptic stimulation protocol, long-term depression (LTD) in synaptic strength was induced at associative, excitatory synapses onto layer II pyramidal neurons of the mouse (P15-27) PC. LTD was mimicked and occluded by mGluR agonists and blocked by nonselective mGluR antagonist (RS)-alpha-methyl-4-sulfonophenylglycine (MSPG) but not by N-methyl-D-aspartic acid (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV). Analysis of the paired-pulse ratio, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA current ratio, and spontaneous EPSCs indicate that electrically induced LTD was mediated predominantly by postsynaptic mechanisms. Additionally, presynaptic mGluRs were involved in agonist-mediated synaptic depression. Immunohistochemical analysis supports the presence of multiple subclasses of mGluRs throughout the PC, with large concentrations of several receptors present in layer II. These observations provide further evidence of activity-dependent, long-term modification of associative inputs and its underlying mechanisms. Cortical adaptation at associative synapses provides an additional link between cortical olfactory processing and subcortical centers that influence behavior.     

Evidence for synchronised responses in the piriform cortex by using Gibbs potential analysis

 The piriform cortex is a large paleocortical area which receives direct projections from the olfactory bulb. In order to study the spatiotemporal distribution of the piriform cortex activity, we chose optical recording of the responses evoked by olfactory bulb electrical stimulation. Such a stimulation elicited a large signal corresponding to cortical reactivation (disynaptic activity) via intrinsic association fibres. As the disynaptic activity was observed over the entire piriform area, we wondered whether or not this redistribution contributes to a synchronisation of the activity in the piriform cortex. In order to answer this question, we developed a statistical approach which allows us to take the temporal dimension into account. The analysis was performed by using the Gibbs potential analysis. The neural response of the diode is represented by a stochastic point process (occurrence of latency peak), and the response of the diode array is given as successive realisations of a binary random field defined on a finite set. The Gibbs measure associated with this field is then estimated through the interaction potentials of the field’s configurations, which provide a quantitative evaluation of the interaction and the synchronisation between the neural sites. The analysis was performed on the latency of the peak of disynaptic activity, which was determined from signals from 60 different acquisitions realised with the same stimulus parameters. From these 60 files of latency values, we estimated the Gibbs interaction potential of singletons and pairs. The former gave an image of the spatiotemporal distribution of the disynaptic activity, which appears to propagate from the anterior to the posterior part of the area recorded. The estimation of the interaction potential of pairs allows us to characterise the degree of synchronisation between two neighbouring recording sites. It appeared that, in the anterior half of the area recorded, the disynaptic activity was statistically desynchronised whereas, in the posterior part the disynaptic activity appeared strongly synchronised. The functional implications of such a spatiotemporal distribution of the activity are discussed. Received : 10 January 1996 / Accepted in revised form: 25 October 1996     

Dissociable codes of odor quality and odorant structure in human piriform cortex

The relationship between odorant structure and odor quality has been a focus of olfactory research for 100 years, although no systematic correlations are yet apparent. Animal studies suggest that topographical representations of odorant structure in olfactory bulb form the perceptual basis of odor quality. Whether central olfactory regions are similarly organized is unclear. Using an olfactory version of fMRI cross-adaptation, we measured neural responses in primary olfactory (piriform) cortex as subjects smelled pairs of odorants systematically differing in quality and molecular functional group (as one critical attribute of odorant structure). Our results indicate a double dissociation in piriform cortex, whereby posterior regions encode quality (but not structure) and anterior regions encode structure (but not quality). The presence of structure-based codes suggests fidelity of sensory information arising from olfactory bulb. In turn, quality-based codes are independent of any simple structural configuration, implying that synthetic mechanisms may underlie our experience of smell.     

Development of dendritic spines in the piriform neurons of the cerebellar cortex in human prenatal ontogeny

The submicroscopic investigation on developmental peculiarities of the dendritic spines in the piriform neurons of the cerebellar cortex has been performed during the human prenatal ontogenesis. The process of morphogenesis of the spines of the tertiary dendrites in the piriform neurons is demonstrated to start rather early--on the 24th week of embryogenesis and goes through three successive stages: 1) formation of a long cytoplasmic processes deprived of any membranous specialization; 2) formation of the terminal spinal head, making synapses with parallel fibers of the cerebellar cortex; 3) definitive stage. A suggestion is made that differentiation processes of the spines depend on inductive influence of the parallel fibers of the cerebellar cortex.     

Open field stress and neurons containing calcium-binding proteins in the piriform cortex of the rat.

In the present study we wanted to check whether the expression of the c-Fos protein (the marker of cellular activity) appears in cells containing calcium-binding proteins (CaBPs) in animals exposed to the open field test. Eight adult Wistar rats were examined. In the first step the open field test was applied throughout 10 minutes. After perfusional fixation brains were frozen and cut on the cryostat in the coronal plane and stained with the standard immunohistochemical method. Sections were double stained for c-Fos and CaBPs: parvalbumin (PV), calbindin (CB), calretinin (CR). c-Fos positive cells were localized predominantly in layers II and III of the piriform cortex (PC). The double labeling study showed that neurons containing CaBPs are rarely c-Fos-immunoreactive. Often PV-positive and CB-positive fibers surround c-Fos-positive neurons in layers II and III in a form of a basket. It seems that cells containing CaBPs are not directly involved in the response to aversive stimuli but cells containing those calcium-binding proteins might influence directly c-Fos positive neurons of PC.     

The piriform cortex and the cortical nucleus of the amygdala in epileptogenesis--the role of the rostrocaudal gradient

The seizure susceptibility of amygdaloid complex in rat was investigated. In piriform cortex and cortical nucleus of amygdaloid complex the structural and electrophysiological rostro-caudal differences were found (using relative spectral densities EEG, seizure thresholds, electrical kindling rate). The fundamental dependence of severity of motor seizures from structural (nuclear or cortical) organization of stimulating area was shown. There were more of limbic stages while stimulating anterior and posterior cortical nuclei, and there were more generalized stages while stimulating piriform and periamygdaloid cortex. Using the model of electrical kindling anticonvulsant effects of Sacricin were demonstrated. Sacricin is one of the compounds of polycarbonic acid. Sacricin has fully coped the process of secondary generalization of epileptic seizures.     

Proliferation of piriform neurons in the rat cerebellar cortex in the pre- and postnatal periods of development]

The method of histoautoradiography with the use of H3-thymidine was applied to the study; there were established the periods of appearance in the cerebellar anlage of albino rats of neuroblasts differentiated into the piriform neurones of the cerebellar cortex; dynamics of the proliferative activity of these cellular elements in the course of the pre- and postnatal periods of development of the experimental animals was investigated. On the basis of the material obtained a conclusion was drawn that the last cell divisions (the result of cell differentiation were Purkinje's cells of the cerebellar cortex) stopped by the 13th--15th day of the embryonic development. No incorporation of the labeled precursor into the DNA of the nuclei of the differentiating piriform neurons occurred later.     

Optical recording of the in vivo piriform cortex responses to electrical stimulation of the lateral olfactory tract in the rat

Using a voltage-sensitive styryl dye, optical recordings ofthe piriform cortex responses to bipolar electrical stimulationsof the rat lateral olfactory tract (LOT) were taken. Surgicalprocedures were performed on Wistar SPF male rats anaesthetizedwith equithesine. Anaesthesia was continued during the recording.In addition the animals were curarized and artificially ventilated.Piriform cortex was stained with RH795. Cortical fluorescencewas recorded with a 124-element photodiode array using epi-illuminationwhile electrical stimulations were delivered to the LOT. Mappingof the piriform activity indicated a very large overlap of therecorded responses. Nevertheless, some differences in locationof recorded responses were observed and seemed to correlatewith the location of the stimulation electrode on the LOT. Theresults are discussed in relation to the anatomy and histologyof the olfactory bulb projections to the piriform cortex.