Subiculum

Only primates have temporal lobes, which are largest in man, accommodating 17% of the cerebral cortex and including areas with auditory, olfactory, vestibular, visual and linguistic functions. Association fibres connect all parts of the cerebral cortex with the parahippocampal gyrus and subiculum, which in turn project to the dentate gyrus. The largest efferent projection of the subiculum and hippocampus is through the fornix to the hypothalamus. http://www.ncbi.nlm.nih.gov/pubmed/22934160

Whole-brain voxel based morphometric analysis found that higher total Lifetime Experiences Questionnaire scores are linked with increased grey matter volume in the medial temporal lobe, especially in the hippocampus. Through a series of more specific analyses, we found that supervisory and managerial experience in midlife was the dominant contributor to this effect. The rate of hippocampal atrophy in late-life in those with high level supervisory experience in midlife was five-times slower than those with no midlife supervisory experience. For the first time, we reveal that managerial and supervisory experience during our working life is connected to hippocampal integrity after retirement, some 20-30 years later. http://www.ncbi.nlm.nih.gov/pubmed/22902920

The medial temporal lobe includes a system of anatomically related structures that are essential for declarative memory (conscious memory for facts and events). http://www.ncbi.nlm.nih.gov/pubmed/15217334

The presubiculum, but not parasubiculum, was strongly reactive for glycogen phosphorylase. These patterns confirm earlier evidence that glycogenolytic demand in Layers I and III of rat entorhinal cortex is organized in a modular fashion and show that such demand can be modified by brief exposure to a novel holeboard. http://www.ncbi.nlm.nih.gov/pubmed/16229987

The anterior thalamic nuclei consist of the anterodorsal (AD), anteroventral, and anteromedial nuclei, each of which are highly differentiated and may contribute to different aspects of various cognitive and memory functions. The data show that the AD provides strong projections to layers I and IV of area 30 and to layers I, III, IV, and VI of area 29 in the retrosplenial cortex, and to layers I and III-VI of the presubiculum. The projections to the presubiculum are not organized topographically. Other minor projections were also observed in the parasubiculum and part of the medial entorhinal area. These results indicate that the AD provides strong projections to the retrosplenial cortex and presubiculum, suggesting that these projections constitute essential pathways to these cortical regions for transmitting mnemonic information, such as a novel conditioning stimulus during the initial stage of avoidance learning. http://www.ncbi.nlm.nih.gov/pubmed/22314639

These findings indicate selective early involvement of the CA1 and subiculum regions of the hippocampus and provide new information on early anterior pole involvement in the entorhinal cortex in incipient AD. http://www.ncbi.nlm.nih.gov/pubmed/22289801

The dorsal presubiculum (also known as the postsubiculum) is critically important for the direct transfer of visual landmark information to spatial signals within the limbic system. http://www.ncbi.nlm.nih.gov/pubmed/21982585

Interestingly, maltreatment was associated with 4.2% and 4.3% reductions in the left presubiculum and subiculum, respectively. http://www.ncbi.nlm.nih.gov/pubmed/22331913

The medial temporal lobe (MTL) encompasses a network of interconnected cortical areas that is considered the neural substrate for some types of memory, such as spatial, episodic, recognition, and associative memory. Within the MTL, the subiculum has been well characterized in terms of its connectivity and structure. However, the dorsal subiculum (DS) is also reciprocally connected to the perirhinal and postrhinal cortices, which are critically involved in recognition memory. This connectivity pattern suggests that DS might encode not only spatial signals but also recognition signals. Theta power was significantly higher in DS when mice explored novel objects as compared to familiar objects and that this theta modulation was absent in CA1. We also detected DS units that were responsive specifically to novel object exploration, indicating that a subset of DS neurons were tuned to novelty during the NOR task. http://www.ncbi.nlm.nih.gov/pubmed/22833721

Synaptic glutamate signaling in brain is highly complex and includes multiple interacting receptors, modulating cotransmitters and distinct regional dynamics. Hippocampal imaging studies in schizophrenia have identified 2 alterations in MTL - increases in baseline blood perfusion and decreases in task-related activation. These observations along with converging postsynaptic hippocampal protein changes suggest that homeostatic plasticity mechanisms might be altered in schizophrenia hippocampus. If hippocampal pattern separation is diminished due to partial dentate gyrus failure (resulting in "spurious associations") and also if pattern completion is accelerated and increasingly inaccurate due to increased CA3 associational activity, then it is conceivable that associations could be false and, especially if driven by anxiety or stress, could generate psychotic content, with the mistaken associations being laid down in memory, despite their psychotic content, especially delusions and thought disorder. http://www.ncbi.nlm.nih.gov/pubmed/22532703

ERPs were recorded in epilepsy patients from multicontact depth electrodes, implanted along the longitudinal axis of MTL. Patients had to respond to rare visual target stimuli by a button press. Target detection resulted in large MTL-P300 potentials in the hippocampus and subiculum. Their latencies did not differ. The hippocampal P300 amplitude increased linearly from anterior to posterior hippocampal body (HB). In contrast, an inverse gradient with larger mean amplitudes in anterior parts was observed for the subiculum. Our results indicate two separate generators of the MTL-P300, one in the anterior subiculum and one in the posterior HB. Since latencies did not differ, a parallel activation via the entorhinal cortex might have initiated the simultaneous MTL-P300. Hippocampus and subiculum are essential parts of the MTL-memory system. Their function within target detection might be to maintain a template of previous stimuli for a comparison with incoming sensory stimuli. http://www.ncbi.nlm.nih.gov/pubmed/19437422

The firing pattern of the ensemble of MTL neurons showed robust temporal autocorrelation over macroscopic periods of time during performance of the memory task. The gradually-changing part of the ensemble state was causally affected by the visual stimulus being presented. Critically, repetition of a stimulus caused the ensemble to elicit a pattern of activity that resembled the pattern of activity present before the initial presentation of the stimulus. These findings confirm a direct prediction of this class of temporal context models and may be a signature of the mechanism that underlies the experience of episodic memory as mental time travel. http://www.ncbi.nlm.nih.gov/pubmed/22488671

Objective perceptual identity correlated with activity in the left MTL, while subjective memory experience correlated with activity in the right MTL for both types of material. http://www.ncbi.nlm.nih.gov/pubmed/22230115

When a subject judged the word as "old," a second judgment was made concerning the physical similarity of the two pictures. Repetition related changes in MTL activation varied depending on whether or not subjects could correctly state that pictures were different. Moreover, psychophysiological interactions analyses showed that accuracy in recalling whether the two pictures were different was predicted by repetition-related changes in the functional connectivity of MTL with frontal regions. Specifically, correct recollection was predicted by increased connectivity between the left posterior hippocampus and the right inferior frontal gyrus, and also by decreased connectivity between the left posterior hippocampus and the left precentral gyrus on the second stimulus presentation. http://www.ncbi.nlm.nih.gov/pubmed/22807169

The role of the subiculum within the behavioural inhibition system. It receives information about available goals from areas that plan motor action. This is filtered by earlier elements of the essentially unidirectional hippocampal circuit that essentially block familiar and unimportant information while passing to the subiculum important information. The function of the subiculum is to compare and integrate this goal information and produce output when conflict between incompatible goals is detected. This output prevents execution of the responses that would address the conflicting goals, increases the valence of affectively negative stimuli and associations and releases external exploration and internal rumination intended to resolve the conflict. These subicular outputs are held to be computationally simple but to have complex consequences both because of the complexity of the target areas and because, in many cases, processing is recursive. It can involve multiple passages of essentially the same information round loops such as the circuit of Papez--each pass refining the solution to the original problem of conflicting goals. http://www.ncbi.nlm.nih.gov/pubmed/16887202

The most prominent cortical projections from the dorsal CA1 and the dorsal parts of the subicular complex are to the retrosplenial and anterior cingulated cortices in rats and monkeys — two cortical regions involved primarily in the cognitive processing of visuospatial information and memory processing  and environmental exploration (spatial navigation) in rats, monkeys, and humans. Meanwhile, the dorsal (but not ventral) parts of this subicular complex send massive parallel projections through the postcommissural fornix to the medial and lateral mammillary nuclei and the anterior thalamic complex — two structures containing the most navigation-related neurons . In turn, these subcortical structures send their projections back to the DH and retrosplennial cortex . It is apparent that this neural network, composed of the dorsal CA1-dorsal subicular complex-mammillary body—anterior thalamic nuclei, provides the most important interface to register a cognitive map for the navigation/direction system, thus, enabling animals to properly orient and execute behaviors in a learned environment. Additionally, the dorsal CA1 and dorsal CA3 project rather selectively to the caudal part (LSc) and tiny dorsal region of the medial zone of the rostral part (LSr.m.d) of the lateral septal nucleus, which in turn projects to the medial septal complex and supramammillary nucleus — two structures that generate and control the hippocampal theta rhythm activated during voluntary locomotion. Furthermore, the dorsal subiculum and lateral band of the lateral and medial entorhinal cortex send massive projections to the rostrolateral part of the nucleus accumbens and rostral caudoputamen, both of which send descending projections either directly, or indirectly via the substantia innominata (ventral pallidum) or globus pallidus (dorsal pallidum), to innervate the ventral tegmental area and/or reticular part of the substantial nigra (SNr). The ventral tegmental area plays a critical role in locomotion, while the SNr mediates in orienting movements of the eyes, head, neck and even upper limbs, via its massive projection to the deeper layers of the superior colliculus. Additionally, the ventral CA1/subiculum and these amygdalar nuclei also share intimate bi-directional connectivity with the infralimbic, prelimbic and agranular insular cortices. These ventral hippocampal/subicular-amygdalar-medial prefrontal cortical structures form a series of parallel, segregated descending projections, either directly or indirectly through the lateral septum (rostral and ventral parts), the medial and central amygdalar nuclei, and bed nuclei of the stria terminalis (BST), to innervate the periventricular and medial zones of the hypothalamus — the primary structure involved in the control of neuroendocrine, autonomic, and somatic motor activities associated with three basic classes of motivated behaviors having strong emotional components: ingestion (feeding and drinking), reproduction (sexual and parental), and defense. It is worth noting that the ventral CA1, along with the ventral subiculum and medial band of the lateral and medial entorhinal cortical areas, also gives rise to direct projections to the caudomedial (shell) nucleus accumbens (but not the rostral and lateral parts), which plays a critical role in reward processing and motivation of feeding behavior. Finally, axonal terminals of the ventral CA1 and ventral subiculum overlap with the circadian-rhythm related inputs from the suprachiasmatic nucleus of the hypothalamic subparaventricular zone and dorsomedial hypothalamic nucleus — two brain structures recently shown to control the sleep-wake circadian circle. The latter two structures may provide a critical interface for the hippocampal inputs to influence general behavioral states and affect. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822727/

The impairing effects of chronic WIN on short-term memory in the water maze and the object recognition tasks as well as long-term potentiation (LTP) in the ventral subiculum (vSub)-nucleus accumbens (NAc) pathway were temporary as they lasted only 24 h or 10 d after withdrawal. http://www.ncbi.nlm.nih.gov/pubmed/22348124

In the aversive contextual fear task, WIN into the basolateral amygdala impaired fear acquisition/consolidation, but not retrieval. In the ventral subiculum (vSub), WIN impaired fear retrieval. In the neutral social discrimination task, WIN into the vSub impaired both acquisition/consolidation and retrieval, whereas in the medial amygdala WIN impaired acquisition. http://www.ncbi.nlm.nih.gov/pubmed/21447623

In adults, TRPC4 expression was high throughout the frontal cortex, lateral septum (LS), pyramidal cell layer of the hippocampus (HIP), dentate gyrus (DG), and ventral subiculum (vSUB). Patch-clamp recording indicated a strong metabotropic glutamate-activated cation current-mediated depolarization that was dependent on intracellular Ca(2+)and inhibited by protein kinase C in brain regions associated with dense TRPC4. http://www.ncbi.nlm.nih.gov/pubmed/17593972

Cells that moderately express alpha2 mRNA were localized to the cerebral cortex layers V and VI, the subiculum, the oriens layer of CA1, the medial septum, the diagonal band complex, the substantia innominata, and the amygdala of both animals. http://www.ncbi.nlm.nih.gov/pubmed/16255031

Small islands of alpha7 immunoreactive cells were present in the outer presubiculum. alpha4 and beta2, and alpha3, alpha4 and beta2 immunoreactive fibre tracts were present in the stratum radiatum and subiculum, respectively, suggesting nAChRs may play a role in modulating inputs to the hippocampus via Schaffer collaterals and along the perforant pathway. Some astrocytes were immunoreactive for alpha3, alpha7 and beta4 subunits. Immunoreactivity to all subunits was noted in association with blood vessels. http://www.ncbi.nlm.nih.gov/pubmed/12663058

When the area of myelination was expressed relative to brain weight, there was a twofold increase between the first and second decades. The increased staining of myelin during the first and second decades principally occurred in the subicular region and adjacent portions of the presubiculum. http://www.ncbi.nlm.nih.gov/pubmed/8192550

We observed a reduction in the numerical density of parvalbumin- and somatostatin-positive interneurons in the caudal EC and parasubiculum in BPD-I and SZ, but no change in the subiculum. http://www.ncbi.nlm.nih.gov/pubmed/21968533

We found that thickness in the entorhinal (ERC) and subicular (Sub) cortices of mild cognitive impairment subjects at initial assessment correlated to change in memory encoding over two years in early stages of neurodegeneration in AD. http://www.ncbi.nlm.nih.gov/pubmed/21559183

We demonstrate that genetic deletion of the beta-secretase (BACE1) not only abrogates Abeta generation and blocks amyloid deposition but also prevents neuron loss found in the cerebral cortex and subiculum, brain regions manifesting the most severe amyloidosis. http://www.ncbi.nlm.nih.gov/pubmed/17258906

The left hippocampal volume was significantly smaller in e4-carriers than non-carriers, the effect of APOE4 mapping to the subicular/CA1 region. http://www.ncbi.nlm.nih.gov/pubmed/21224004

Our primary thesis is that the encoding of short-term memories into new, long-term memories represents the collective set of nonlinearities induced by the three or four principal subsystems of the hippocampus, i.e., entorhinal cortex-to-dentate gyrus, dentate gyrus-to-CA3 pyramidal cell region, CA3-to-CA1 pyramidal cell region, and CA1-to-subicular cortex. http://www.ncbi.nlm.nih.gov/pubmed/20700470

Higher visual medial temporal atrophy rating scale scores were associated with progressive atrophy of the subiculum and the CA1-3 subregions. http://www.ncbi.nlm.nih.gov/pubmed/20143386

A local map of the animal's surroundings is stored in CA1 and subicular regions, where matching of fragment positions and attributes takes place. http://www.ncbi.nlm.nih.gov/pubmed/1308181

The present results highlight the susceptibility of subicular plasticity to acute stress and provide evidence that GR activation is necessary but not sufficient for mediating these alterations. http://www.ncbi.nlm.nih.gov/pubmed/22918985

Spatial information outflow from the hippocampal circuit: distributed spatial coding and phase precession in the subiculum. Remarkably, despite the disparate firing rate properties of subicular neurons, we found that neurons at all proximal-distal locations exhibit robust theta phase precession, with similar spiking oscillation frequencies as neurons in area CA1. http://www.ncbi.nlm.nih.gov/pubmed/22915100

Subjects with amnestic mild cognitive impairment exhibited significant hippocampal volume reductions in the presubiculum, subiculum and cornu ammonis 2-3 areas compared with healthy subjects. http://www.ncbi.nlm.nih.gov/pubmed/22759884

According to their spiking pattern, pyramidal cells in the subiculum were classified as bursting cells and non-bursting cells. In the present study, we demonstrate that subicular bursting cells show input-specific forms of long-term potentiation (LTP). At CA1-Sub synapses, bursting cells have been shown to express a presynaptic NMDA receptor-dependent LTP that depends on the activation of a cAMP-PKA cascade (Wozny et al., Journal of Physiology 2008). In contrast, at EC-Sub synapses the induction of LTP in bursting cells shows a high induction-threshold and relies on the activation of postsynaptic NMDA receptors, postsynaptic depolarization and postsynaptic Ca(2+) influx. Each form of LTP is input-specific and fails to induce heterosynaptic plasticity. http://www.ncbi.nlm.nih.gov/pubmed/22104348

Here we show using a complete rat hippocampal preparation in vitro that the subiculum intrinsically and independently generates spontaneous slow (25-50 Hz) and fast (100-150 Hz) gamma rhythms during the rising phase and peak of persistent subicular theta rhythms. These two gamma frequencies are phase modulated by theta rhythms without any form of afferent input from the entorhinal cortex or CA1. Fast GABAergic inhibition is required for the generation of fast gamma, whereas slow gamma is generated by excitatory and inhibitory mechanisms. In addition, the transverse subicular axis exhibits gamma rhythm topography with faster gamma coupling arising in the distal subiculum region. These results suggest the subiculum is a third spontaneous gamma generator in the hippocampal formation (in addition to CA3 and the entorhinal cortex). http://www.ncbi.nlm.nih.gov/pubmed/21865453

We used single and paired intracellular patch clamp recordings from post-hoc-identified cells in acute rat hippocampal slices and identified a subpopulation of molecular layer interneurons that expressed immunocytochemical markers present in members of the neurogliaform cell (NGFC) class. Single NGFCs displayed small dendritic trees, and their characteristically dense axonal arborizations covered significant portions of the outer and middle one-thirds of the molecular layer, with frequent axonal projections across the fissure into the CA1 and subicular regions. http://www.ncbi.nlm.nih.gov/pubmed/21452204

Ventral subicular lesioning impaired the spatial task performances in rats and produced considerable degree of dendritic atrophy of the hippocampal pyramidal neuron. http://www.ncbi.nlm.nih.gov/pubmed/21074573

Using high-resolution fMRI (1.6 mm × 1.6-mm in-plane), we found that activity within the right CA23DG increased during encoding compared to retrieval. Conversely, right subicular activity increased during retrieval compared to encoding of spatial associations. http://www.ncbi.nlm.nih.gov/pubmed/20882543

Apoptotic neurons were detected in the subicular region of both suicide and Addison victims, and it is statistically significant in both right and left between the cases. The present study confirms the vulnerability of the subicular neurons to apoptosis, possibly due to corticosteroids in both ends of spectrum. http://www.ncbi.nlm.nih.gov/pubmed/20048453

In contrast to CA1 pyramidal cells, bursting pyramidal cells in the subiculum showed a Na(+) spike-evoked medium afterhyperpolarizations that was reduced by apamin, indicating cell-type-dependent differences in mAHP mechanisms. http://www.ncbi.nlm.nih.gov/pubmed/18684909

With antibodies raised against the N-terminal mouse EAAT4 sequence, the highest protein expression levels were observed in the substantia nigra pars compacta, ventral tegmental area, paranigral nucleus, habenulo-interpeduncular system, supraoptic nucleus, lateral posterior thalamic nucleus, subiculum, and superficial layers of the superior colliculus. http://www.ncbi.nlm.nih.gov/pubmed/18770868

Ventral subiculum (vSUB) lesions enhance corticosterone responses to psychogenic stressors via trans-synaptic influences on paraventricular nucleus (PVN) neurons. Synaptic relays likely occur in GABA-rich regions interconnecting the vSUB and PVN. Exposure to novelty stress increased c-fos mRNA expression in the PVN to a greater degree in vSUB lesion relative to shams, consistent with an inhibitory role for the vSUB in the HPA stress response.  vSUB lesions increased GAD65 or GAD67 mRNA levels in several efferent targets, including anterior and posterior subnuclei of the bed nucleus of the stria terminalis and lateral septum. Lesions did not effect stress-induced increases in GAD65 expression in principal output nuclei of the amygdala. The current data suggest that loss of vSUB innervations produces a compensatory increase in GAD expression in subcortical targets; however, this up-regulation is insufficient to block lesion-induced stress hyperresponsiveness, perhaps driven by amygdalar disinhibition of the PVN. http://www.ncbi.nlm.nih.gov/pubmed/16979601

The ventral subiculum (vSUB) is an interface between the hippocampal formation and structures in the brain reward circuitry, such as the nucleus accumbens (NAc) and prefrontal cortex (PFC). The vSUB powerfully activates the dopamine system, particularly in response to novelty. This activity is both necessary and sufficient to elevate nucleus accumbens dopamine levels triggered by a novel stimulus. Direct stimulation of the vSUB increases the population of active dopamine neurons in the ventral tegmental area and dopamine levels in the accumbens via a multisynaptic route relayed through the nucleus accumbens. Furthermore, activity in the vSUB is correlated with drug-seeking behaviour such that vSUB inhibition attenuates cocaine-primed reinstatement of drug-seeking, while brief vSUB activation triggers reinstatement cocaine-seeking.  We report that acute cocaine alters vSUB pyramidal neuron activity by inducing a frequency-dependent output mode transition from bursting to single-spiking. We suggest that under normal conditions bursting and output mode switching (bursting to single-spiking) may be needed for proper routing of information in and out of the vSUB. We propose that psychostimulants disrupt bursting and output mode switching leading to inappropriate dopamine/novelty signaling that is necessary to set motivational states and direct attention and ultimately, behaviour. http://www.ncbi.nlm.nih.gov/pubmed/16870273

Increased excitability enhances the flow of hippocampal output through the subiculum resulting in support for frontal lobe function and the action mode. Decreased excitability, on the other hand, reduces this output and that support, leading to a disconnection between frontal lobes and hippocampus. At the same time, correlated cholinergic activity enhances receptive mode processes, indicated by the occurrence of the hippocampal theta rhythm. It is suggested that the hypothesis provides a conceptual framework for considering various phenomena including REM sleep, schizophrenia, and hypnosis. In REM sleep the receptive mode remains dominant as cholinergic activity supports the hippocampal integration of experience into a composite view of reality. In schizophrenia, the action and receptive modes are not properly coordinated because of a dysfunction in anterior hippocampal output. http://www.ncbi.nlm.nih.gov/pubmed/16824701

In addition, inactivating the vSub with TTX attenuates the ability of the BLA to drive spike firing in the NAc. Thus, the vSub is required for activation of the NAc by the BLA. http://www.ncbi.nlm.nih.gov/pubmed/21211108

The ventral subiculum (vSUB), a hippocampal efferent target implicated in learning and stress coping, receives cholinergic input and sends glutamatergic output to the bed nucleus of the stria terminalis (BNST). Results of the 1-day retention tests showed that intra-vSUB infusion of oxotremorine (0.01 microg) or scopolamine (0.3 or 3.0 microg) enhanced or impaired retention, respectively. These data suggest that in an inhibitory avoidance task muscarinic activation of the vSUB modulated memory formation by interacting with the BNST glutamatergic and noradrenergic functions. http://www.ncbi.nlm.nih.gov/pubmed/19041726

The ventral subiculum (vSub) of the hippocampus, in particular, is proposed to gate information flow within the NAc, a factor that is disrupted in models of schizophrenia. Using in vivo extracellular recordings in anesthetized rats, we examined the response of NAc neurons to vSub stimulation and how this is modulated by the mPFC. We found that inactivation of mPFC by tetrodotoxin attenuates the ability of the vSub to drive spike firing in the NAc. Thus, a contribution of the mPFC is required for the activation of NAc by the vSub. However, when long-term potentiation is induced in the vSub-NAc pathway, the vSub is now capable of driving the NAc without the participation of the mPFC. Moreover, this interaction is dependent on activation of dopaminergic D(2) receptors in the NAc. This work demonstrates the critical role of the mPFC in the ability of vSub to drive NAc neurons in normal anesthetized animals. One model of schizophrenia posits that vSub hyperactivity may underlie both the hyperdopaminergic state and disruption of information flow in this circuit in schizophrenia. Therefore, inactivation of the mPFC, as would occur with mPFC leukotomy in schizophrenia, may prevent the abnormal vSub drive of the NAc. http://www.ncbi.nlm.nih.gov/pubmed/18815264

D1 receptor antagonism (3.0 nmol/0.5 microl SCH-23390 bilaterally) in the vSUB impaired instrumental learning and performance, reduced break point in progressive ratio (PR) tests, and produced an intrasession decline in responding during test sessions, but had no effect on spontaneous motor or food-directed behavior. D1 activation in the vSUB may be a critical component of motivational arousal associated with learned contextual cues. http://www.ncbi.nlm.nih.gov/pubmed/16768606

In the hippocampal formation (dentate gyrus, hippocampus proper and subiculum) and entorhinal cortex, the colocalization of the 5-HT2Ar with the inhibitory transmitter ?-aminobutyric acid (GABA) was studied using double immunofluorescence confocal microscopy. http://www.ncbi.nlm.nih.gov/pubmed/22119732

Subjects with late life depression exhibited significant hippocampal volume reductions in the total hippocampus, subiculum, and Cornu Ammonis (CA) 2-3 areas compared with healthy subjects. http://www.ncbi.nlm.nih.gov/pubmed/22840623

In hippocampal formation of control subjects, H3 receptor radioligand binding was prominent in dentate gyrus, subiculum, entorhinal cortex and parasubiculum. Decreased H3 binding was found in the CA4 area of bipolar subjects. Decreased H3 binding in CA2 and presubiculum of medication-free bipolar subjects was also seen. http://www.ncbi.nlm.nih.gov/pubmed/19413576

High levels of GalR2 mRNA and protein expression were observed in the presubiculum, subiculum, cingulate cortex, retrosplenial granular and agranular cortices, subregions of prefrontal cortex, and the olfactory bulb, regions which are directly or indirectly implicated in depression-like behavior. http://www.ncbi.nlm.nih.gov/pubmed/21672612

SNAP-25 levels were reduced significantly in stratum oriens of bipolar patients compared with controls (p < 0.05); they were also reduced significantly in st. oriens (p < 0.01 vs schizophrenia), in alveous (p < 0.01 vs schizophrenia) and in presubiculum (p < 0.05 vs depressed). Depressed SNAP-25 levels increased in st. moleculare (p < 0.01 vs schizophrenics) and presubiculum (p < 0.05 vs controls and bipolars; p < 0.01 vs schizophrenics). http://www.ncbi.nlm.nih.gov/pubmed/11711867

The findings also suggest further functional differences within retrosplenial subregions as area 29 received the large majority of efferents from the subiculum. http://www.ncbi.nlm.nih.gov/pubmed/22522494

Somatostatin messenger RNA (mRNA) is rapidly but transiently expressed de novo in pyramidal neurons of the subiculum and entorhinal cortex 24 hours after KA. Surviving somatostatin interneurons display increased mRNA levels at late intervals (3 months) after KA and increased labeling of their terminals in the outer molecular layer of the subiculum; the labeling correlates with the number of spontaneous seizures, suggesting that the seizures may trigger somatostatin expression. In contrast, neuropeptide Y mRNA is consistently expressed in principal neurons of the proximal subiculum and the lateral entorhinal cortex and labeling for the peptide persistently increased in virtually all major excitatory pathways of the hippocampal formation. The pronounced plastic changes differentially involving both neuropeptide systems indicate marked rearrangement of parahippocampal areas, presumably aiming at endogenous seizure protection. http://www.ncbi.nlm.nih.gov/pubmed/22437342

We conclude that the deep layer cells of the presubiculum and parasubiculum are richly interconnected with excitatory synapses. These interconnections can generate giant excitatory synaptic potentials that support the bursting behaviour exhibited by these neurons. Any of the excitatory inputs to deep layer cells can trigger the population bursts and specific inputs from entorhinal cortex produce the after-discharges. http://www.ncbi.nlm.nih.gov/pubmed/9192310

We found that subicular projections to each area were composed of a mixture of regular-spiking and bursting neurons. Neurons projecting to amygdala, lateral entorhinal cortex, nucleus accumbens, and medial/ventral orbitofrontal cortex were located primarily in the proximal subiculum and consisted mostly of regular-spiking neurons (~80%). By contrast, neurons projecting to medial EC, presubiculum, retrosplenial cortex, and ventromedial hypothalamus were located primarily in the distal subiculum and consisted mostly of bursting neurons (~80%). Neurons projecting to a thalamic nucleus were located in the middle portion of subiculum, and their probability of bursting was close to 50%. http://www.ncbi.nlm.nih.gov/pubmed/21538658

This, possibly novel, TTX-I sodium current could contribute to the coding functions of presubicular neurons, specifically the maintained firing associated with signalling of a stable head position. http://www.ncbi.nlm.nih.gov/pubmed/19596892

Saturation binding and displacement experiments showed that [(125)I]YVP and [(125)I]EYF bound selectively with a very high affinity, K(D)=0.18 nM and 0.06 nM, to NPFF(1) and NPFF(2) receptors respectively.The highest densities of [(125)I]EYF binding sites were seen in the most external layers of the dorsal horn of the spinal cord, the parafascicular thalamic nucleus, laterodorsal thalamic nucleus and presubiculum of hippocampus. http://www.ncbi.nlm.nih.gov/pubmed/12421602

Vesicular glutamate transporter 1 (VGluT1) is one of the best markers for glutamatergic neurons, because it accumulates transmitter glutamate into synaptic vesicles. Differentiation-associated Na(+)-dependent inorganic phosphate cotransporter (DNPI) shows 82% amino acid identity to VGluT1, and is another candidate for vesicular glutamate transporters. Both DNPI and VGluT1 immunoreactivities were found mostly in neuropil, presumably in axon terminals, throughout the brain. In the telencephalic regions, intense DNPI immunoreactivity was observed in the glomeruli of the olfactory bulb, layer IV of the neocortex, granular layer of the dentate gyrus, presubiculum, and postsubiculum. In contrast, VGluT1 immunoreactivity was intense in the olfactory tubercle, layers I-III of the neocortex, piriform cortex, entorhinal cortex, hippocampus, dentate gyrus, and subiculum. http://www.ncbi.nlm.nih.gov/pubmed/11835181

The regions of highest V1a receptor density included the prefrontal, cingulate, pyriform, and entorhinal cortex, as well as the presubiculum and mamillary bodies. http://www.ncbi.nlm.nih.gov/pubmed/10223283

The parasubiculum and the external principal lamina of the presubiculum may be the structures most vulnerable to early lesions in the parahippocampal gyrus in CJD. http://www.ncbi.nlm.nih.gov/pubmed/9988133