• A major focus is laid on addressing signalling mechanisms which underlie activity-dependent changes in primary sensory neurons transmitting pain (nociceptors) and their synapses in the spinal dorsal horn. (uni-heidelberg.de)
  • Plasticity of primary sensory neurons and of the synapses tey make with dorsal horn neurons is an important component of the cellular basis for the development and maintenance of chronic, pathogenic pain. (uni-heidelberg.de)
  • In addition to the olfactory neurons, the epithelium is composed of supporting cells, Bowman glands and ducts unique to the olfactory epithelium, and basal cells that allow for the regeneration of the epithelium, including the olfactory sensory neurons. (medscape.com)
  • In effect, the gatekeeper neuron acts as the transistor of a gated synapse by modulating the transmission of the signal between the pre-synaptic and post-synaptic neurons. (wikipedia.org)
  • Computational analysis from our collaboration with the Raphael and Lysakowski labs (below) suggests that non-quantal transmission occurs by fast current flow through open low-voltage-activated ion channels in both the pre-synaptic hair cell membrane ( K,L channels) and post-synaptic calyx membrane ( Kv1, Kv7, HCN ), and by slower modulation of K+ concentration in the extended synaptic cleft. (uchicago.edu)
  • When in dendrites and spines, βAR 248 was frequently concentrated along plasma membranes and at post-synaptic densities of asymmetric (excitatory) synapses. (frontiersin.org)
  • To understand better the cellular mechanisms of NE's contributions to fear learning, we examined the anatomical organization of NE terminals and βARs in the LA. In this study, we employed immunoelectron microscopy to determine whether terminals immunoreactive for dopamine beta-hydroxylase (DβH), the synthetic enzyme for NE, form synaptic junctions in the LA and if so, examine these synapses and identify the post-synaptic targets on NE terminals. (frontiersin.org)
  • STP implies that the response of a post-synaptic neuron depends of the history of presynaptic activity, creating information that in principle can be extracted and used. (scholarpedia.org)
  • Following a spike, (i) \(u\) increases due to spike-induced calcium influx to the presynaptic terminal, after which (ii) a fraction \(u\) of available resources is consumed to produce the post-synaptic current. (scholarpedia.org)
  • Selective inhibition of certain synapses has been studied thoroughly (see Gate theory of pain), and recent studies have supported the existence of permissively gated synaptic transmission. (wikipedia.org)
  • Several current projects are directed at elucidating novel mediators of synaptic plasticity at synapses between primary afferents and spinal neurons. (uni-heidelberg.de)
  • These synapses use both quantal transmission: glutamate release from synaptic vesicles clustered at presynaptic ribbons , and novel non-quantal transmission. (uchicago.edu)
  • Short-term plasticity (STP) ( Stevens 95 , Markram 96 , Abbott 97 , Zucker 02 , Abbott 04 ), also called dynamical synapses, refers to a phenomenon in which synaptic efficacy changes over time in a way that reflects the history of presynaptic activity. (scholarpedia.org)
  • Consequently, the intrinsic properties and pairwise interactions of their constituent neurons can be characterized, including analyses of their communication via gap junctions, action potential-gated synapses or graded synapses. (degruyter.com)
  • 26. Comparison of cellular mechanisms of long-term depression of synaptic strength at perforant path-granule cell and Schaffer collateral-CA1 synapses. (elsevier.com)
  • The afferent signal travels across the sensory nerve to the relay synapses in the spinal cord, a process called conduction. (reviewofoptometry.com)
  • These forms of plasticity are due to increases in presynaptic neurotransmitter release, and can be engaged when dentate GCs fire in bursts (e.g., during exploratory behaviors) and bring CA3 pyramidal neurons above threshold. (eneuro.org)
  • Our working hypotheses are based on the relevance of specific identifiable network topologies as well as patterns of synaptic transmission for the functional capacity of a network in terms of plasticity, learning, and adaptability and, by the same token, for the initiation and spread of lesion-related pathologies in vivo and in vitro. (ntnu.edu)
  • The aim of our study was to identify molecular changes produced by prenatal exposure to WIN 55,212-2 that might contribute to late disruption in synaptic plasticity and cognition. (researchgate.net)
  • Second, these antibodies impair the induction of synaptic plasticity, rebound potentiation, and LTD, on Purkinje cells, resulting in loss of restoration and compensation of the distorted "internal models. (springer.com)
  • For example, we have generated a mouse line which enables deletion of genes specifically in all nociceptive neurons of the dorsal root ganglia (DRG) and trigeminal ganglia without affecting gene expression in non-nociceptive neurons, the spinal cord, the brain or any other organs in the body (Agarwal et al. (uni-heidelberg.de)
  • Central sensitization is a process whereby nociceptive neurons and circuits exhibit increased function in response to activity, inflammation, or injury through a variety of processes that include changes in receptor field size, increases in neuronal excitability, increases in synaptic efficiency/coupling, and changes in neuronal connectivity ( Latremoliere and Woolf, 2009 ). (nature.com)
  • External stimulation of the NMDA receptors is responsible for moving the neuron from the down state to the up state, while the stimulation of AMPA receptors allows the neuron to reach and surpass the threshold potential. (wikipedia.org)
  • Furthermore, we have recently reported that synaptic proteins of the Homer1 family, which interconnect metabotropic glutamate receptors (mGluR1/5) with intracellular calcium stores, are important modulators of inflammatory pain. (uni-heidelberg.de)
  • To understand better the cellular mechanisms of NE and its adrenergic receptors in the LA, we used antibodies directed against dopamine beta-hydroxylase (DβH), the synthetic enzyme for NE, or against two different isoforms of the beta-adrenergic receptors (βARs), one that predominately recognizes neurons (βAR 248) and the other astrocytes (βAR 404), to characterize the microenvironments of DβH and βAR. (frontiersin.org)
  • These data highlight the important integrative role played by parasympathetic ganglia and indicate that activation of NK 3 receptors in airway ganglia by endogenous neurokinins facilitates synaptic neurotransmission. (johnshopkins.edu)
  • Here we demonstrate that similar activity amplification occurs in mice, and that this is related to suppressed inhibition to PB neurons from the central nucleus of the amygdala (CeA) in animals of either sex. (iasp-pain.org)
  • We describe a novel pathway, consisting of inhibition by dynorphin, somatostatin and corticotropin-releasing hormone expressing neurons in the central nucleus of the amygdala that project to the parabrachial nucleus (PB). (iasp-pain.org)
  • Considered collectively, the findings demonstrate that LTP FC involves (1) elevation of [K + ] o in the DH s , (2) NMDAR activation, and (3) conversion of the effect of GABA on DH s neurons from inhibition to excitation. (en-journal.org)
  • First, since chained inhibitory neurons shape the output signals through the mechanism of disinhibition/inhibition, impairments of GABA release and LTD distort the conversion process from the "internal model" to the output signals. (springer.com)
  • Central to this role is the inhibitory action exerted by Golgi cells over granule cells: Golgi cells inhibit granule cells through both feedforward and feedback inhibitory loops and generate a broad lateral inhibition that extends beyond the afferent synaptic field. (amrita.edu)
  • ipRGCs use vesicular glutamate transporter 2 (vGlut2) to package glutamate into synaptic vesicles and light-evoked resetting of the SCN circadian clock is widely attributed to ipRGC glutamatergic neurotransmission. (eneuro.org)
  • Our results demonstrate that the amplitude of spontaneous miniature and evoked EPSCs in nTS neurons is significantly increased in Mecp2 -null mice and, accordingly, that mutant cells are more likely than wild- type cells to fire action potentials in response to primary afferent stimulation. (jneurosci.org)
  • The present study demonstrates that nTS relay neurons in Mecp2 -null mice exhibit significantly larger EPSCs, and are more likely to fire action potentials in response to afferent stimulation, than in wild-type controls. (jneurosci.org)
  • In the pathway between the PFC and the hippocampus, stimulation of mediodorsal thalamic neurons, as well as stimulation of ventral tegmental area neurons inhibited PFC neuron firing. (wikipedia.org)
  • Therefore, we hypothesized that nTS neurons in Mecp2 -null mice would exhibit exaggerated responses to primary afferent stimulation due to loss of this BDNF-dependent modulation. (jneurosci.org)
  • Sensory afferents have been incorporated in the model to study the effects of afferent stimulation on locomotor phase switching and step cycle period and on the firing patterns of flexor and extensor motoneurones. (nih.gov)
  • The model also suggests that the different effects of flexor muscle nerve afferent stimulation observed experimentally (phase prolongation versus resetting) result from opposing influences of flexor group I and II afferents on the PF and RG circuits controlling the activity of flexor and extensor motoneurones. (nih.gov)
  • The purpose of the present study was to determine whether neurokinins, released during axonal reflexes or after antidromic afferent nerve stimulation, modulate ganglionic synaptic neurotransmission. (johnshopkins.edu)
  • Intracellular recordings from the ganglia neurons revealed that capsaicin-sensitive nerve stimulation potentiated subsequent preganglionic nerve-evoked fast excitatory postsynaptic potentials. (johnshopkins.edu)
  • To date, Kirupa's research has broadly focused on neurons within the auditory efferent circuit, which allow the brain to modulate incoming sound signals at the ear. (aro.org)
  • Examples of this kind of gating have been found in visual cortical neurons and areas of the prefrontal cortex (PFC) in primates that may be responsible for suppressing irrelevant stimuli. (wikipedia.org)
  • By using a combination of optogenetics, in vivo electrophysiology, and machine learning analysis, we find that a subset of neurons in the ACC receives S1 inputs, and activation of the S1 axon terminals increases the response to noxious stimuli in ACC neurons. (iasp-pain.org)
  • LSD augmentation may be representative of synaptic facilitation, suggesting increased reactivity of the visual pathway to afferent stimuli. (erowid.org)
  • Intrageniculate serotonin, a putative inhibitory transmitter in LGN, decreased each component of the CVEP and TVEP, suggesting both a net decrease inthalamocortical transmission and attenuation of Intrageniculate responses to light stimuli. (erowid.org)
  • It has been reported that long-term enhancement of superficial dorsal horn (DH s ) excitatory synaptic transmission underlies central sensitization, secondary hyperalgesia, and persistent pain. (en-journal.org)
  • Clearly, therefore, establishment of the long-term enhancement of DH s excitatory synaptic transmission that underlies central sensitization, secondary hyperalgesia, and persistent pain does not, as previously believed, require a sustained preceding period of high-frequency nociceptor afferent activation. (en-journal.org)
  • The experiments described in this paper were motivated by the intriguing and clinically relevant possibility that a long-term enhancement of DH s excitatory synaptic transmission not only can occur in the absence of a preceding period of conditioning afferent drive (as described above), but can arise subsequent to an impairment of DH s glial energy metabolism. (en-journal.org)
  • Chronic pain enhances this cortico-cortical connection, as manifested by an increased number of ACC neurons that respond to S1 inputs and the magnified contribution of these neurons to the nociceptive response in the ACC. (iasp-pain.org)
  • The current work determines how and where opioids modulate synaptic transmission between the thalamic, cortical and striatal regions that are important for the perception of affective pain. (elifesciences.org)
  • Results revealed opposing roles of the MORs and DORs regarding information flow from the thalamus to the striatum, whereby MOR activation decreased glutamate transmission in the striatum, while DOR activation facilitated glutamate transmission via disinhibition of cortical pyramidal neurons. (elifesciences.org)
  • Avendaño C, Rausell E, Perez-Aguilar D, Isorna S (1988) Organization of the association cortical afferent connections of area 5: a retrograde tracer study in the cat. (yale.edu)
  • Our laboratories use biophysical, electrophysiological, molecular biological and histological methods to determine fundamental molecular mechanisms by which neurotransmitters are released from primary sensory cells ('hair cells') to excite second order neurons carrying information to the brain. (hopkinsmedicine.org)
  • BoNT/A-mediated cleavage of SNAP-25 in the FN is prevented by intracerebroventricular delivery of antitoxin antibodies, demonstrating that BoNT/A physically leaves the motoneurons to enter second-order neurons. (jneurosci.org)
  • When activated, the gatekeeper neuron alters the polarity of the presynaptic axon to either open or close the gate. (wikipedia.org)
  • If this neuron depolarizes the presynaptic axon, it allows the signal to be transmitted. (wikipedia.org)
  • Neuronal density of GPi (3.00 ± 0.13 × 10(3) neurons/mm(3)) and GPe (3.62 ± 0.22 × 10(3) neurons/mm(3)) yields a mean ratio of ChAT+ axon varicosities per pallidal neuron of 74 ± 10 in the GPi and 128 ± 28 in the GPe. (ulaval.ca)
  • STD is caused by depletion of neurotransmitters consumed during the synaptic signaling process at the axon terminal of a pre-synaptic neuron, whereas STF is caused by influx of calcium into the axon terminal after spike generation, which increases the release probability of neurotransmitters. (scholarpedia.org)
  • This study examined opioid actions on glutamate transmission between these brain regions in mouse. (elifesciences.org)
  • However, this synaptopathy is associated with decreased BDNF availability in the primary afferent pathway and can be rescued by application of exogenous BDNF. (jneurosci.org)
  • Although much is known about the activation of escape circuitry by the primary afferent inputs that signal approach of predators, such as acoustic,acousticolateralis, visual and mechanosensory inputs, far less is known about how the same circuits are engaged by abiotic stressors such as high or low temperature, or anoxia. (biologists.com)
  • Our lab is using dendritic patch clamp recordings to examine mechanisms of synaptic transmission at this first, critical synapse in the auditory pathway. (hopkinsmedicine.org)
  • The vestibular inner ear encodes head motion and position in signals initiated and shaped by mechanosensitive and voltage-gated ion channels of sensory receptor cells (hair cells), transmitted by extraordinary mechanisms to afferent neurons, and translated into spike trains by voltage-gated ion channels at spike initiation zones adjacent to the afferent terminals. (uchicago.edu)
  • C, Several current projects concern the roles of specific ion channels in synaptic transmission mechanisms at the synapse between HCI and afferent calyx terminals. (uchicago.edu)
  • Our findings provide a morphological basis for understanding ways in which NE may modulate transmission by acting via synaptic or non-synaptic mechanisms in the LA. (frontiersin.org)
  • Notably, the mechanisms that link synaptic dysfunction with the manifestations of CAs can be explained by disruption of the "internal models. (springer.com)
  • 25. Control of synaptic consolidation in the dentate gyrus: mechanisms, functions, and therapeutic implications. (elsevier.com)
  • Bal T, von Krosigk M, McCormick DA (1995) Synaptic and membrane mechanisms underlying synchronized oscillations in the ferret lateral geniculate nucleus in vitro. (yale.edu)
  • Destexhe A, Babloyantz A, Sejnowski TJ (1993) Ionic mechanisms for intrinsic slow oscillations in thalamic relay neurons. (yale.edu)
  • While this study demonstrates that TRPV1 of the dorsal root ganglia (DRG) neurons modulate nociceptive behaviors, the role of the TRPV1 in supraspinal brain structures was not investigated. (biomedcentral.com)
  • it affects the output signal of the postsynaptic neuron. (wikipedia.org)
  • Postsynaptic responses in the afferent terminals arrive at hemi-nodes where they initiate spike trains that propagate along the nerve fibers through cell bodies ( vestibular ganglion neurons, VGNs ) and on to central targets in the brainstem and cerebellum. (uchicago.edu)
  • Whether it is turned on or off is dependent on the nature of the input signal (either excitatory or inhibitory) from the presynaptic neuron. (wikipedia.org)
  • 2016). We extend these results here by showing that the probability of presynaptic vesicular release is reduced when an uncleaved α 2 δ is expressed in rat neurons and that this inhibitory effect is reversed when cleavage of α 2 δ is restored. (elifesciences.org)
  • Indeed, we show that uncleaved α 2 δ−1 inhibits presynaptic calcium transient-triggered action potential (AP) in hippocampal neurons and that this effect is reversed by the cleavage of α 2 δ−1. (elifesciences.org)
  • Without continued presynaptic activity, the synaptic efficacy will quickly return to its baseline level. (scholarpedia.org)
  • Synaptic gating is the ability of neural circuits to gate inputs by either suppressing or facilitating specific synaptic activity. (wikipedia.org)
  • To approach these issues, we analyzed synaptic function in the brainstem nucleus tractus solitarius (nTS), the principal site for integration of primary visceral afferent inputs to central autonomic pathways and a region in which we found markedly reduced levels of BDNF in Mecp2 mutants. (jneurosci.org)
  • PB neurons in CCI-Pain animals showed a reduction in inhibitory, GABAergic inputs. (iasp-pain.org)
  • We show that-in both rats and mice-PB contains few GABAergic neurons, and that most of its GABAergic inputs arise from CeA. (iasp-pain.org)
  • In contrast, intraraphe serotonin may increase the tonic inhibitory influence of raphe on LGN, thus decreasing LGN neuronal reaponsiveneasto visual afferent inputs. (erowid.org)
  • Thermal and infection stress inputs to the preoptic area of the hypothalamus dynamically alter the DMH→rMR transmission to elicit thermoregulatory, febrile, and cardiovascular responses. (mpg.de)
  • Mu-opioid receptor (MOR) agonists potently inhibited MThal inputs without affecting ACC inputs to individual striatal medium spiny neurons (MSNs). (elifesciences.org)
  • MOR activation also inhibited MThal inputs to the pyramidal neurons in the ACC. (elifesciences.org)
  • In contrast, delta-opioid receptor (DOR) agonists disinhibited ACC pyramidal neuron responses to MThal inputs by suppressing local feed-forward GABA signaling from parvalbumin-positive interneurons. (elifesciences.org)
  • As a result, DOR activation in the ACC facilitated poly-synaptic (thalamo-cortico-striatal) excitation of MSNs by MThal inputs. (elifesciences.org)
  • Confocal microscopy revealed that both excitatory and inhibitory neurons express βAR248. (frontiersin.org)
  • Anti-GAD65 antibody (Ab) acts on the terminals of inhibitory neurons that suppress GABA release, whereas anti-VGCC, anti-mGluR1, and anti-GluR Abs impair LTD induction. (springer.com)
  • These design features include the involvement of relatively large neurons that conduct neural information rapidly, but that have a relatively high threshold for activation. (biologists.com)
  • In autoimmune limbic encephalitis, it is assumed that these auto-antibodies diffusely interfere with basal synaptic transmission or neural excitability and weaken overall functions of the temporal lobe [ 18 ]. (springer.com)
  • Signals from central and peripheral zones on the sensory epithelium are shaped differentially by distinct complements of ion channels in both hair cells and afferent neurons. (uchicago.edu)
  • Among the three families of Ca V channels (Ca V 1, Ca V 2 and Ca V 3), the Ca V 2 family and more specifically Ca V 2.1 and Ca V 2.2 channels (generating P/Q and N-type currents, respectively) are particularly important for synaptic transmission in central and peripheral nervous systems ( Dolphin, 2012 ). (elifesciences.org)
  • Pathways for ocular pain originate from a peripheral stimulus that then travels to the central nervous system along the afferent pathway. (reviewofoptometry.com)
  • We show that this pathway regulates the activity of pain-related neurons in PB, and that, in chronic pain, this inhibitory pathway is suppressed, and that this suppression is causally related to pain perception. (iasp-pain.org)
  • In addition, there are normally relatively few synaptic connections in the pathway from sensory input to motor output and these connections, often involving an electrical component, have a high fidelity to ensure fail safe transmission. (biologists.com)
  • These CeA GABA neurons express dynorphin, somatostatin and/or corticotropin releasing hormone. (iasp-pain.org)
  • Whole-cell patch recordings were carried out to evaluate the effects of FC on the response of DH s neurons to puffer-applied GABA. (en-journal.org)
  • 1 hr) depolarizing shift of the equilibrium potential for the DH s neuron transmembrane ionic currents evoked by GABA. (en-journal.org)
  • GAD65 is involved in the synthesis, packaging, and release of GABA, whereas the other three play important roles in the induction of long-term depression (LTD). Thus, the auto-antibodies toward these synaptic molecules likely impair fundamental synaptic machineries involved in unique functions of the cerebellum, potentially leading to the development of cerebellar ataxias (CAs). (springer.com)
  • A, In the sensory epithelium of the rodent utricle, a simple sensory map of two zones (a central striola and surrounding extrastriola, ES ) provides natural access to basic questions of how hair cells and afferent neurons generate, transmit, and propagate sensory signals. (uchicago.edu)
  • It blocks neurotransmission via the specific cleavage of the synaptic protein SNAP-25 (synaptosomal-associated protein of 25 kDa). (jneurosci.org)
  • Neurons, the basic unit of the brain serves as messengers inside the body through the process of neurotransmission. (infomory.com)
  • The presence of auto-antibodies that target synaptic machinery proteins was documented recently in immune-mediated cerebellar ataxias. (springer.com)
  • Bistable neurons have the ability to oscillate between a hyperpolarized (down state) and a depolarized (up state) resting membrane potential without firing an action potential. (wikipedia.org)
  • Neurons that have this bistable ability have the potential to be gated because outside gatekeeper neurons can modulate the membrane potential of the gated neuron by selectively shifting them from the up state to the down state. (wikipedia.org)
  • Animals with pain after chronic constriction injury of the infraorbital nerve (CCI-Pain) displayed higher spontaneous and evoked activity in PB neurons, and a dramatic increase in after-discharges-responses that far outlast the stimulus-compared to controls. (iasp-pain.org)
  • aspartate receptor-mediated synaptic responses in hippocampal CA1 neurons. (tocris.com)
  • To analyze the transformation of sensory signals by ion channels at each processing stage, we use the whole-cell method of patch clamping to record currents and voltages from individual hair cells, afferent terminals, and neuronal cell bodies in intact rodent vestibular epithelia. (uchicago.edu)
  • B, Utricular hair cells of 2 types ( HC I and II ) transduce linear head accelerations and head tilt into receptor potentials, which drive transmission across highly specialized calyx and bouton afferent terminals. (uchicago.edu)
  • Generally, this input occurs in the form of neuromodulatory substances, such as hormones, neuropeptides and other neurotransmitters that have been released from incoming neurons. (wikipedia.org)
  • Ib afferent fibers causes excitation of antagonist muscles. (symptoma.com)
  • E. Ia afferent fibers causes excitation of muscles on the contralateral side. (symptoma.com)
  • These afferent signals contribute to our sense of heading and drive fast, accurate reflexes that stabilize vision and balance as we move. (uchicago.edu)
  • For many years an outstanding question in vestibular physiology was how the transduction current in the type I hair cell was sufficient, in the face of large conductances on at rest, to depolarize it to potentials necessary for conventional synaptic transmission with its unique afferent calyx. (aro.org)
  • In collaboration with Dr. Art, I overcame the technical challenges of simultaneously recording from type I hair cells and their enveloping calyx afferent to investigate this question. (aro.org)
  • Cell assemblies and central pattern generators (CPGs) are related types of neuronal networks: both consist of interacting groups of neurons whose collective activities lead to defined functional outputs. (degruyter.com)
  • Hearing researcher Amanda Lauer - whose work is supported through the David M. Rubenstein Hearing Center - explains how she uses electron microscopy to examine synaptic and nanoscale structures. (hopkinsmedicine.org)
  • We have used a scanning transmission electron microscopy dataset of a whole Drosophila larva to elucidate the central sensory-motor circuit that controls swallowing and its coordination with the enteric nervous system. (mpg.de)
  • Under starvation stress, medullary reticular neurons activated by hunger signaling from the hypothalamus suppress thermogenic drive from the rMR for energy saving and prime mastication to promote food intake. (mpg.de)
  • In general, synaptic gating involves a mechanism of central control over neuronal output. (wikipedia.org)
  • Nucleus tractus solitarius (NTS) is the central integration hub for afferents from upper airway (somatosensory/gustatory), respiratory, gastrointestinal, cardiovascular (baroreceptor and chemoreceptor) and other systems. (hindawi.com)
  • it may also affect central circuits directly via axonal trafficking and transfer to upstream neurons (transcytosis). (jneurosci.org)
  • Each region in the central nervous system is endowed with particular synaptic machinery types of proper properties for delivering the region-specific functions. (springer.com)
  • However, the identity of central serotonergic neurons and the neuronal circuits within which they are embedded are largely unknown at single cell and synaptic level. (mpg.de)
  • Their afferent signal is conveyed onto a set of central serotonergic neurons that project back out via the larval vagus nerve and facilitates swallowing motor pattern. (mpg.de)
  • During the extensor phase of fictive locomotion, activation of extensor muscle group I afferents increases extensor motoneurone activity and prolongs the extensor phase. (nih.gov)
  • Our data indicate that the proteolytic maturation increases the association of α 2 δ−1 with Ca V channel complex and is essential for its function on synaptic release. (elifesciences.org)
  • A depressant effect of LSD on the raphe nucleus, an area which tonically inhibits forebrain structures via 5-HT release, would effect disinhibition reaulting in increased LGN to cortex transmission, evidenced by increased CVEP. (erowid.org)