Spatiotemporal distribution of a late synchronized activity in olfactory pathways following stimulation of the olfactory bulb in rats

The evoked potential recorded in the rat piriform cortex in response to electrical stimulation of the olfactory bulb is composed of an early component occasionally followed by a late component (60–70 ms). We previously showed that the late component occurrence was enhanced following an olfactory learning. In the present study carried out in naive rats, we investigated the precise conditions of induction of this late component, and its spatiotemporal distribution along the olfactory pathways. In the anaesthetized rat, a stimulating electrode was implanted in the olfactory bulb. Four recording electrodes were positioned, respectively, in the olfactory bulb, the anterior and posterior parts of the piriform cortex, and the entorhinal cortex. Simultaneous recording of signals evoked in the four sampled structures in response to stimulation of the olfactory bulb revealed that the late component was detected in anterior and posterior piriform cortex as well as in entorhinal cortex, but not in the olfactory bulb. The late component occurred reliably for a narrow range of low intensities of stimulation delivered at frequencies not exceeding 1 Hz. Comparison of late component amplitude and latency across the different recorded sites showed that this component appeared first and with the greatest amplitude in the posterior piriform cortex. In addition to showing a functional dissociation between anterior and posterior parts of the piriform cortex, these data suggest that the posterior piriform cortex could be the locus of generation of this late high amplitude synchronized activity, which would then propagate to the neighbouring regions.     

Associative Synaptic Potentials in the Piriform Cortex of the Isolated Guinea-pig Brain In Vitro

The involvement of local and remote associative fibres in the generation of piriform cortex synaptic potentials was investigated in the isolated guinea-pig brain maintained in vitro by arterial perfusion by implementing current source density analysis (CSD) on cortical field potential profiles. Previous hypotheses were verified using acute surgical isolation of piriform cortical areas to study different synaptic events separately. Stimulation of the lateral olfactory tract activated associative potentials throughout the piriform cortex. In the anterior piriform cortex, the current sinks responsible for the generation of associative potentials were located in the superficial portion of layer lb and in layer III. In the posterior piriform cortex, two associative events were observed: an early sink located in the superficial part of layer Ib, followed by a sink in the deep part of the same layer. In the anterior piriform cortex, local associative synaptic potentials were separated from the component carried by long projective fibres by surgically isolating a small area of cortex monosynaptically activated by lateral olfactory tract stimulation. In this patch of lateral olfactory tract-connected anterior piriform cortex, local associative sinks were observed in the superficial lb layer and in layer III. Monosynaptic activation of the isolated patch of anterior piriform cortex induced purely associative potentials throughout the piriform cortex. These potentials were mediated by the synaptic activation of apical dendrites in the superficial lb layer and selectively abolished by severing the long associative fibres. The anterior piriform cortex layer III sink and the posterior piriform cortex deep lb associative component were evoked by the activation of large population spikes in the monosynaptic anterior piriform cortex and the disynaptic posterior piriform cortex response respectively. These two sinks are presumably generated locally through a polysynaptic circuit, whose activation depends on the degree of cortical excitation. Olfactory signal processing in the guinea-pig piriform cortex during states of normal excitability is supported by the interactions between associative inputs impinging on the synapses located separately on the dendrites of pyramidal neurons. An increase in the synchronization of piriform cortex neuron discharge activates usually silent local circuit synapses.     

Piriform cortex functional heterogeneity revealed by cellular responses to odours

The role of the piriform cortex (PC) in olfactory information processing remains mainly unknown. Indeed, until recently, only a few studies have investigated the response of PC neurons to odours and these studies did not take into account the functional heterogeneity of the PC previously described using an electrical stimulation paradigm. In this experiment, extracellular activity in response to odour was recorded in urethane anaesthetized rats in the different parts of the cortex ranging from anterior to posterior. A large percentage of cortical cells were silent at rest, and this percentage increased from anterior to posterior. Analysis of odour evoked activity revealed a large percentage of nonresponsive cells that increased from anterior to posterior. Cell activity was largely synchronized with breathing and different temporal patterns were observed. The anterior PC was characterized by odour-evoked responses phase-locked with the inhalation-exhalation transition period. By contrast, activity in the posterior PC was mainly phase-locked with inhalation or exhalation. These data confirm the spatial functional heterogeneity previously reported in the PC. Functional anatomy of the PC suggests that activity in the anterior PC can be mainly driven by afferent activity coming from the OB whereas posterior cells were certainly entrained by more complex mechanisms.     

Expression of Fos in the piriform cortex after acquisition of olfactory learning: An immunohistochemical study in the rat

The piriform cortex (PCx), the main area of the primary olfactory cortex, is assumed to play a role in olfactory memory. Involvement of this paleocortex in mnesic processes was investigated by using Fos immunocytochemistry after acquisition of a two-odor discrimination task. Trained rats had to associate one odor of a pair with water reward while pseudo-trained rats were randomly rewarded. We further used non-trained rats and home cage control animals to determine the effect of manipulation and basal Fos level respectively. Except in control rats, Fos immunoreactivity was mainly distributed in brain areas involved in olfactory processing, learning and arousal. The trained, pseudo-trained, and non-trained rats showed a high Fos labeling in the entire PCx. However, quantitative analysis demonstrated a statistically higher Fos immunoreactivity in the anterior PCx in comparison with the posterior PCx for these rats. Furthermore, behavioral data allowed us to distinguish two groups of trained rats according to the number of days required to acquire the task. Rats with slow acquisition showed a higher Fos immunoreactivity in the whole PCx in comparison with the rats exhibiting a fast acquisition. Our findings support the assumption of a PCx rostro-caudal heterogeneity which could sustain differential information processing.     

Learning-induced Changes in Rat Piriform Cortex Activity Mapped Using Multisite Recording With Voltage Sensitive Dye

The piriform cortex (PCx) has a potential role in storage and recall of olfactory information. This study is a first extensive investigation of the spatiotemporal distribution of activity in the PCx induced by learned sensory inputs following conditioning. In a conditioned group, rats chronically implanted with four electrodes in the olfactory bulb were trained to associate the electrical stimulation of a given bulbar electrode with a positive reinforcement, while stimulation of a different electrode predicted a negative reinforcement. In a familiarized group, rats received the same protocol of daily electrical stimulation with no associated reinforcement. At the end of the conditioning or familiarization episode, activity evoked in the PCx was optically mapped using a 144 photodiode array. In the anaesthetized rats, PCx maps were recorded in response to stimulation of each of the four bulbar electrodes using either high (0.5–1 mA) or low (0.1 mA) test current intensities. Low intensity stimulation revealed that conditioning selectively enhanced the probability of occurrence of a signal composed of a single late (56–73 ms) component which occurred almost simultaneously on a large PCx area. In the conditioned group, high intensity stimulation through either of the four electrodes revealed a potentiation of the early (17–30 ms) disynaptic component of the PCx response in the most posterior part of the PCx as well as a homogeneous increase of the late (39–52 ms) component spread over the PCx areas. These data suggest that learning induces synaptic changes at different nodes of the PCx circuitry.     

Bulbar projecting subcortical GABAergic neurons send collateral branches extensively and selectively to primary olfactory cortical regions

Circuit operations of the olfactory bulb are modulated by higher order projections from multiple regions, many of which are themselves targets of bulbar output. Multiple glutamatergic regions project to the olfactory bulb, including the anterior olfactory nucleus (AON), prefrontal cortex (PFC), piriform cortex (PC), entorhinal cortex (EC), and tenia tecta (TT). In contrast, only one region provides GABAergic projections to the bulb. These GABA neurons are located in the horizontal limb of the diagonal band of Broca extending posteriorly through the magnocellular preoptic nucleus to the nucleus of the lateral olfactory bulb. However, it was unclear whether bulbar projecting GABAergic neurons collaterallize projecting to other brain regions. To address this, we mapped collateral projections from bulbar projecting GABAergic neurons using intersectional strategies of viral and traditional tract tracers. This approach revealed bulbar projecting GABAergic neurons show remarkable specificity targeting other primary olfactory cortical regions exhibiting abundant collateral projections into the accessory olfactory bulb, AON, PFC, PC, and TT. The only "nonolfactory" region receiving collateral projections was sparse connectivity to the medial prefrontal orbital cortex. This suggests that basal forebrain inhibitory feedback also modulates glutamatergic feedback areas that are themselves prominent bulbar projection regions. Thus, inhibitory feedback may be simultaneously modulating both synaptic processing of olfactory information in the bulb and associational processing of olfactory information from primary olfactory cortex. We hypothesize that these olfactory GABAergic feedback neurons are a regulator of the entire olfactory system.     

The laminar distribution of intracortical fibers originating in the olfactory cortex of the rat

In this study, the autoradiographic method for tracing axonal connections was used to identify the laminar distribution of intracortical fibers originating in the olfactory cortical areas of the rat. Most of the projections can be divided into two major fiber systems with different laminar patterns of termination. The first of these, termed the layer Ib fiber system, arises in the anterior olfactory nucleus, the anterior and posterior piriform cortex, and the lateral entorhinal cortex, and terminates predominantly in layer Ib and, in many cases, layer III of the entire olfactory cortex. The second system, termed the layer II-deep Ib fiber system, originates in three relatively small olfactory cortical areas-the dorsal peduncular cortex, the ventral tenia tecta, and the periamygdaloid cortex and terminates in and around the cells of layer II in most parts of the olfactory cortex. There is significant overlap in the laminar distribution of the two systems, although the distinction between them is readily apparent. Within the layer Ib fiber system there are relatively slight but consistent differences in the lamination of fibers from different areas. The fibers from the anterior olfactory nucleus are concentrated in the deep part of layer Ib while those from the anterior piriform cortex are concentrated in the superficial part of this layer. The fibers from the posterior piriform cortex tend to be densest in the middle of layer Ib. These differences are maintained in all areas of termination of each set of fibers, both ipsilaterally and contra-laterally. In addition, intracortical fibers from the anterior cortical nucleus of the amygdala are distributed throughout layer I, including layer la and Ib. Fibers from the nucleus of the lateral olfactory tract terminate bilaterally around the cells of the islands of Callej a and the medial edge of the anterior piriform cortex.     

Coding of peripheral electrical stimulation frequency in thalamocortical pathways

Frequency information of the environment is an important feature for sensory perception. It has been demonstrated that cortical and thalamic neurons exhibited frequency-specific responses to peripheral stimulation. In the present study, we investigated the effects of 1-100 Hz peripheral electrical stimulations on various thalamic and cortical areas in awake rats. We used chronically implanted microelectrode arrays to record neural activities from the anterior cingulate cortex, primary somatosensory cortex, and medial dorsal and ventral posterior thalamus. The results revealed that cortical and thalamic neurons exhibited frequency-specific responses at both single-neuron and ensemble levels. Clusters of neurons responded to different frequency ranges with changes of both the peak firing rates and the phases of the peak responses in a stimulation cycle. Partial directed coherence analysis showed that information flowing between these recorded areas is also enhanced or inhibited in some frequency-specific pattern during stimulation. These evidences suggest that central nervous system may code environmental frequency information mainly with the activation of selected neural circuits according to their own intrinsic electrical properties. These properties, in turn, may facilitate or inhibit their responses when stimulation with specific frequency information arrives.     

Taste-olfactory convergence, and the representation of the pleasantness of flavour, in the human brain

The functional architecture of the central taste and olfactory systems in primates provides evidence that the convergence of taste and smell information onto single neurons is realized in the caudal orbitofrontal cortex (and immediately adjacent agranular insula). These higher-order association cortical areas thus support flavour processing. Much less is known, however, about homologous regions in the human cortex, or how taste-odour interactions, and thus flavour perception, are implemented in the human brain. We performed an event-related fMRI study to investigate where in the human brain these interactions between taste and odour stimuli (administered retronasally) may be realized. The brain regions that were activated by both taste and smell included parts of the caudal orbitofrontal cortex, amygdala, insular cortex and adjoining areas, and anterior cingulate cortex. It was shown that a small part of the anterior (putatively agranular) insula responds to unimodal taste and to unimodal olfactory stimuli, and that a part of the anterior frontal operculum is a unimodal taste area (putatively primary taste cortex) not activated by olfactory stimuli. Activations to combined olfactory and taste stimuli where there was little or no activation to either alone (providing positive evidence for interactions between the olfactory and taste inputs) were found in a lateral anterior part of the orbitofrontal cortex. Correlations with consonance ratings for the smell and taste combinations, and for their pleasantness, were found in a medial anterior part of the orbitofrontal cortex. These results provide evidence on the neural substrate for the convergence of taste and olfactory stimuli to produce flavour in humans, and where the pleasantness of flavour is represented in the human brain.     

Intrinsic subthreshold oscillations of the membrane potential in pyramidal neurons of the olfactory amygdala

The amygdala complex is a heterogeneous group of temporal lobe brain structures involved in the processing of biologically significant sensory stimuli and in the generation of appropriate responses to them. The amygdala has also been implicated in certain forms of emotional learning and memory. While much progress has been made in understanding neural processing in the basolateral subgroup of the amygdala, physiological studies in the cortical regions of the complex, also known as olfactory amygdala, are missing. Using a rat brain slice preparation, we conducted whole-cell recordings on pyramidal neurons of the periamygdaloid cortex and the anterior cortical nucleus, two structures receiving direct connections from the olfactory bulb. Upon depolarization by current injection through the recording electrode, a fraction of periamygdaloid cortex and most anterior cortical nucleus layer II pyramidal neurons displayed an intermittent discharge pattern, where clusters of action potentials were interspersed by periods of membrane potential subthreshold oscillations. Oscillations frequency increased with membrane potential and correlated linearly with the cluster spiking frequency. Frequency ranged from 3 to 20 Hz, considering different cells and membrane potential values (up to approximately 30 mV above resting potentials of typically approximately -70 mV). Subthreshold oscillations were preserved after pharmacological inhibition of fast excitatory and inhibitory synaptic transmission, but were abolished by application of the sodium channel blocker tetrodotoxin. We conclude that pyramidal neurons of the olfactory cortical amygdala display intrinsically generated voltage-dependent membrane potential rhythmic fluctuations in the theta-low beta range, requiring the activation of a sodium conductance.     

Corticotropin-releasing factor acting at the locus coeruleus disrupts thalamic and cortical sensory-evoked responses

Stress and stress-related psychiatric disorders, including post-traumatic stress disorder, are associated with disruptions in sensory information processing. The neuropeptide, corticotropin-releasing factor (CRF), coordinates the physiological and behavioral responses to stress, in part, by activating the locus coeruleus-norepinephrine (LC-NE) projection system. Although the LC-NE system is an important modulator of sensory information processing, to date, the consequences of CRF activation of this system on sensory signal processing are poorly understood. The current study examined the dose-dependent actions of CRF at the LC on spontaneous and sensory-evoked discharge of neurons within the thalamus and cortex of the vibrissa somatosensory system in the awake, freely moving rat. Peri-LC infusions of CRF resulted in a dose-dependent suppression of sensory-evoked discharge in ventral posterior medial thalamic and barrel field cortical neurons. A concurrent increase in spontaneous activity was observed. This latter action is generally not found with iontophoretic application of NE to target neurons or stimulation of the LC-NE pathway. Net decreases in signal-to-noise of sensory-evoked responses within both regions suggest that under conditions associated with CRF release at the LC, including stress, the transfer of afferent information within sensory systems is impaired. Acutely, a suppression of certain types of sensory information may represent an adaptive response to an immediate unexpected stressor. Persistence of such effects could contribute to abnormalities of information processing seen in sensorimotor gating associated with stress and stress-related psychopathology.     

Distribution of neuropeptide S receptor mRNA and neurochemical characteristics of neuropeptide S-expressing neurons in the rat brain

Neuropeptide S (NPS) and its receptor (NPSR) constitute a novel neuropeptide system that is involved in regulating arousal and anxiety. The NPS precursor mRNA is highly expressed in a previously undescribed group of neurons located between the locus coeruleus (LC) and Barrington's nucleus. We report here that the majority of NPS-expressing neurons in the LC area and the principal sensory trigeminal nucleus are glutamatergic neurons, whereas many NPS-positive neurons in the lateral parabrachial nucleus coexpress corticotropin-releasing factor (CRF). In addition, we describe a comprehensive map of NPSR mRNA expression in the rat brain. High levels of expression are found in areas involved in olfactory processing, including the anterior olfactory nucleus, the endopiriform nucleus, and the piriform cortex. NPSR mRNA is expressed in several regions mediating anxiety responses, including the amygdaloid complex and the paraventricular hypothalamic nucleus. NPSR mRNA is also found in multiple key regions of sleep neurocircuitries, such as the thalamus, the hypothalamus, and the preoptic region. In addition, NPSR mRNA is strongly expressed in major output and input regions of hippocampus, including the parahippocampal regions, the lateral entorhinal cortex, and the retrosplenial agranular cortex. Multiple hypothalamic nuclei, including the dorsomedial and the ventromedial hypothalamic nucleus and the posterior arcuate nucleus, express high levels of NPSR mRNA, indicating that NPS may regulate energy homeostasis. These data suggest that the NPS system may play a key role in modulating a variety of physiological functions, especially arousal, anxiety, learning and memory, and energy balance.     

Modulation of the piriform cortex activity by the basal forebrain: an optical recording study in the rat

The piriform cortex (PCx) is the main projection area of the olfactory bulb. It further receives afferents from neurons located in the horizontal limb of the diagonal band (HDB) and the magnocellular preoptic nucleus (MCPO) of the basal forebrain. Using an optical recording technique, we examined the influence of electrical stimulation of the HDB-MCPO complex upon the PCx reactivity to electrical stimulation of the olfactory bulb. We observed an inhibitory modulation which was stronger on the intrinsic activity than on the afferent one. This effect was not homogeneously distributed within the whole PCx. The neurotransmitter involved and its synaptic target remain to be determined. The present findings are discussed in view of anatomical and functional data.     

Lesion of the lateral entorhinal cortex amplifies odor-induced expression of c-fos, junB, and zif 268 mRNA in rat brain

Paradoxical facilitation of olfactory learning following entorhinal cortex (EC) lesion has been described, which may result from widespread functional alterations taking place within the olfactory system. To test this hypothesis, expression of the immediate early genes c-fos, junB, and zif 268 was studied in response to an olfactory stimulation in several brain areas in control and in EC-lesioned rats. Olfactory stimulation in control rats induced the expression of the three genes in the granular/mitral and glomerular layers of the olfactory bulb, as well as c-fos and junB expression in the piriform cortex. However EC lesion was devoid of effects in nonstimulated animals; it significantly amplified the odor-induced expression of the three genes in these areas, as well as in the amygdala, hippocampus, and parietal-temporal cortices. The data suggest that EC lesion modifies the neural processing of odor by suppressing an inhibitory influence on brain areas connected to this cortex.     

Interactions between Associative Synaptic Potentials in the Piriform Cortex of the In Vitro Isolated Guinea Pig Brain

The interaction between synaptic potentials generated by the activation of separate sets of associative fibres was investigated in the piriform cortex of an in vitro isolated guinea pig brain preparation. Restricted regions of the piriform cortex served by separate contingents of afferent fibres of the lateral olfactory tract were isolated surgically. The activity generated by these patches of cortex in response to afferent stimulation propagates to remote cortical regions along cortico-cortical associative fibres. Current source density (CSD) analysis of field potential laminar profiles evoked by lateral olfactory tract stimulation confirmed that the synaptic sinks induced by distinct associative fibre contingents converge on the apical dendrites of piriform cortex neurons in the superficial lb layer. Pairing between potentials evoked by activation of two separate sets of associative fibres resulted in an almost linear summation when the two responses coincided. For interstimulus intervals of <100 ms, heterosynaptic pairing of independent associative inputs induced a facilitation of the conditioned associative potential, which correlated with an increase in the associative sink located in layer lb, as demonstrated by CSD analysis. The evaluation of the pairing intervals suggests that the heterosynaptic facilitation of the conditioned associative potentials may be due to the summation of local and remote associative synaptic events. It is concluded that separate associative inputs converge on the apical dendrites of piriform cortex pyramidal neurons to generate synaptic potentials through the activation of spatially close but independent synapses. The role of associative synaptic integration in the functional organization of the olfactory cortex is discussed.     

The development of axonal connections in the central olfactory system of rats

The development of the cytoarchitecture and axonal connections of the central olfactory system were studied in fetal and neonatal rats from E16. In contrast to neocortical development, the olfactory cortex lacks a distinct cortical plate. In the piriform cortex and the olfactory tubercle the cellular laminae emerge simultaneously, while in the anterior olfactory nucleus, there are morphogenetic gradients from superficial to deep as well as from caudal to rostral which parallel the known cytogenetic gradients. Parallel morphogenetic and cytogenetic gradients are also present in the lateral to medial axis of the olfactory tubercle. The projection from the olfactory bulb and the associational projections from the piriform cortex begin to develop well before birth. At E17 fibers from the bulb are limited to the lateral olfactory tract (LOT) and the molecular layer just deep to it, and then spread out caudally, laterally, and medially away from the LOT. This sequence of innervation parallels and predicts the density of innervation in the adult: those areas which are innervated first (such as the piriform cortex deep to the LOT) ultimately receive the heaviest innervation; conversely, those areas which are innervated very late (such as the medial olfactory tubercle) receive the lightest projection. The intracortical projections from the anterior and posterior piriform cortex extend into layer I ipsilaterally by E20 and obtain their adult distribution by the middle of the first postnatal week. On the other hand, fibers from the anterior olfactory nucleus and the entorhinal area do not reach their full adult extent until the second postnatal week. Similarly, the crossed projection of the anterior piriform cortex to the contralateral posterior piriform cortex does not grow into layer I until this later time. The timing of fiber ingrowth showed no relation to the trajectory or eventual areal or laminar termination of fibers. As with the olfactory bulb projection, the timing may influence the density of termination. Centrifugal fibers to the bulb are demonstrable around the time of birth both by the retrograde transport of horseradish peroxidase (HRP) and by the anterograde transport of 3H-leucine. The arrival of additional fibers during the remainder of the first postnatal week parallels the known cytogenetic and morphogenetic gradients in the areas in which they arise. The projections of the olfactory cortex to the lateral hypothalamic area and the mediodorsal thalamic nucleus are evident before birth. This correlates with the early generation of the cells which give rise to these projections.     

Modified coeruleo-cortical noradrenergic neurotransmission after serotonin depletion by PCPA: electrophysiological studies in the rat

To detect eventual modifications in the efficacy of the noradrenergic (NA) coeruleo-cortical system after serotonin (5-HT) depletion by parachlorophenylalanine (PCPA), three electrophysiological parameters were investigated in urethane-anesthetized rats which were treated for 2 days with daily injections of this inhibitor of 5-HT synthesis. 1) The spontaneous activity of locus coeruleus (LC) noradrenergic neurons showed a significant increase in PCPA-treated compared to control rats (4.3 vs. 2.6 Hz). 2) The sensitivity of NA autoreceptors was measured in the LC by the effect of intravenous administrations of clonidine or microiontophoretic applications of NA on spontaneous neuronal firing. In treated rats, clonidine and NA induced a lesser reduction of LC neuron firing than in the controls (27 vs. 75% decreases and 1,367 vs. 280 nC, respectively). 3) The responsiveness of cortical neurons to electrical stimulation of the LC was assessed by peristimulus time histograms in the dorsal fronto-parietal cortex. Following stimulation at 2 or 4 Hz, a majority of spontaneously firing cortical units was inhibited by electrical stimulation of the LC, but the percentage of such units was reduced and showed a decreased responsiveness after PCPA treatment. These findings suggest that following 5-HT depletion by PCPA, cortical NA neurotransmission is markedly reduced in its efficacy in spite of some increase in the spontaneous activity of coeruleo-cortical NA neurons.     

Secreted TARSH regulates olfactory mitral cell dendritic complexity

Olfactory sensory neurons synapse with mitral cells to form stereotyped connections in the olfactory bulb (OB). Mitral cell apical dendrites receive input from olfactory sensory neurons expressing the same odorant receptor. During development, this restricted dendritic targeting of mitral cells is achieved through eliminating elaborated dendritic trees to a single apical dendrite. Through a genome-wide microarray screen, we identified TARSH (Target of NESH SH3) as a transiently expressed molecule in mitral cells during the dendritic refinement period. TARSH expression is restricted to pyramidal neurons along the main olfactory pathway, including the anterior olfactory nucleus and piriform cortex. The dynamic TARSH expression is not altered when odor-evoked activity is blocked by naris closure or in AC3 knockout mice. We also demonstrate that TARSH is a secreted protein. In dissociated OB cultures, secreted TARSH promotes the reduction of mitral cell dendritic complexity and restricts dendritic branching and outgrowth of interneurons. Dendritic morphological changes were also observed in mitral cells overexpressing TARSH themselves. We propose that TARSH is part of the genetic program that regulates mitral cell dendritic refinement.     

Biological complexity and adaptability of simple mammalian olfactory memory systems

Chemosensory systems play vital roles in the lives of most mammals, including the detection and identification of predators, as well as sex and reproductive status and the identification of individual conspecifics. All of these capabilities require a process of recognition involving a combination of innate (kairomonal/pheromonal) and learned responses. Across very different phylogenies, the mechanisms for pheromonal and odour learning have much in common. They are frequently associated with plasticity of GABA-ergic feedback at the initial level of processing the chemosensory information, which enhances its pattern separation capability. Association of odourant features into an odour object primarily involves anterior piriform cortex for non-social odours. However, the medial amygdala appears to be involved in both the recognition of social odours and their association with chemosensory information sensed by the vomeronasal system. Unusually not only the sensory neurons themselves, but also the GABA-ergic interneurons in the olfactory bulb are continually being replaced, with implications for the induction and maintenance of learned chemosensory responses.