Disease relevance of Perforant Pathway

• We show here that intrahippocampal administration of SP triggers self-sustaining status epilepticus (SSSE) in response to stimulation of the perforant path for periods too brief to have any effect in control rats, and this SSSE generates a pattern of acute hippocampal damage resembling that known to occur in human epilepsy [1].
• Our studies show that (i) MAP1B is a temporal and regional marker for rapid and acute epileptic seizures and (ii) long-term increases in MAP1B in the perforant path might play a role in PTZ-induced seizures [2].
• They also appeared, however, in the perforant path terminal zone of the hippocampal dentate molecular layer 1-2 days after transient ischemia and in stratum oriens and stratum radiatum of area CA1b prior to somatic degeneration [3].
• This GFAP accumulation occurred 48-72 h after focal brain injury or perforant-path transection (wallerian degeneration) [4].

Psychiatry related information on Perforant Pathway

• Alzheimer's disease: glutamate depletion in the hippocampal perforant pathway zone [5].
• Central infusion of angiotensin IV or its more stable analogues facilitates memory retention and retrieval in normal animals and reverses amnesia induced by scopolamine or by bilateral perforant pathway lesions [6].
• We studied the effects of tau-pathology on the clinical expression of dementia in 106 autopsy cases in the entorhinal region, the hippocampal stratum oriens, the stratum radiatum, and the perforant path target zone [7].

High impact information on Perforant Pathway

• Here we report that weak activation of the perforant path, when given in the presence of arachidonic acid, leads to a slow-onset persistent increase in synaptic efficacy both in vivo and in vitro [8].
• Similarly, in the dentate gyrus (DG), LTP of either the lateral (LPP) or medial (MPP) components of the perforant path afferents has been associated with only short-lasting reciprocal heterosynaptic depression [9].
• Long-term potentiation of the perforant path in vivo is associated with increased glutamate release [10].
• However, electrophysiological studies are now indicating that other elements of the perforant path that project directly to CA1 and CA3 are more important than thought previously, and that the properties of different neuronal elements in the EC may determine the way in which information is passed on to and processed by the hippocampus [11].
• Up regulation of calbindin-D28K mRNA in the rat hippocampus following focal stimulation of the perforant path [12].

Chemical compound and disease context of Perforant Pathway

• GalKO mice showed increased propensity to develop status epilepticus after perforant path stimulation or systemic kainic acid, as well as greater severity of pentylenetetrazol-induced convulsions [13].
• In hippocampal slices from adult rats, paired-pulse stimulation of perforant path axons revealed a persistent enhancement of dentate granule-cell inhibition following KA status epilepticus or kindling [14].
• To characterize the response of ectopic hilar granule cells to perforant path stimulation, intracellular recordings were made in hippocampal slices from rats that had pilocarpine-induced status epilepticus and subsequent spontaneous recurrent seizures [15].
• To analyse the status epilepticus-induced alterations in the amygdaloid circuitries which may later underlie epileptogenesis, we studied the amygdaloid damage in kainic acid and perforant pathway stimulation models of status epilepticus in the rat [16].
• An animal model of self-sustaining status epilepticus (SSSE) induced in rats by brief intermittent perforant path stimulation (PPS) was examined with regard to the effects of two conventional antiepileptic drugs, diazepam and phenytoin [17].

Biological context of Perforant Pathway

• Before the discovery of the metabotropic glutamate receptors (mGluRs), the glutamate analogue L-2-amino-4-phosphonobutanoic acid (L-AP4) was identified as a potent presynaptic inhibitor of evoked synaptic transmission in the lateral perforant pathway in rats [18].
• The NMDA receptor-mediated component of the hippocampal granule cell population excitatory postsynaptic potential response to low frequency (< 0.2 Hz) stimulation of the medial perforant path was characterized in vivo [19].
• Extracellular amino acid levels and field potentials evoked by perforant pathway stimuli were studied in vivo by means of a dialysis device, perfusing the rat dentate gyrus with low chloride solutions [20].
• 3. Treatment of slices with the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-amino-5-phosphonovaleric acid (APV) unmasked dye fluorescence signals in the outer and middle molecular layers corresponding to action potentials in axons, presumably belonging to the perforant path [21].
• Together with previous mRNA data, our observations suggest abundant axoplasmic transport and secretion in pathways such as the retino-collicular tract, the entorhino-hippocampal ('perforant') path, the lateral olfactory tract or the parallel fiber system of the cerebellum [22].

Anatomical context of Perforant Pathway

• Extensive electrical stimulation of the perforant pathway input to the hippocampus results in a characteristic pattern of neuronal death, which is accompanied by an impairment of cognitive functions similar to that seen in human temporal lobe epilepsy [23].
• Extensive lesions in the entorhinal cortex or knife cuts that severed the perforant path caused near elimination of the tone-evoked discharges to both the CS+ and CS-tones [24].
• The progression and permanence of this histological alteration were similarly evaluated during the behavioral and electrographic evolution of kindling evoked by perforant path, amygdala, or olfactory bulb stimulation [25].
• Wild-type and AC1 mutant mice exhibited comparable perforant path LTP recorded in the dentate gyrus as well as decremental LTP at the Schaffer collateral-->CA1 pyramidal cell synapse [26].
• Second, oleate enhancement of LTP was more potent when applied in the perforant path synaptic terminal zone than in the dentate hilus, implying that the site of oleate action is at the synapse (where PKC is reported to be enriched) [27].

Associations of Perforant Pathway with chemical compounds

• Glutamate as transmitter of hippocampal perforant path [28].
• Electrophysiological recordings from dentate granule cells revealed that high-frequency stimulation of perforant path afferents induced a robust STP and LTP of both (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor-mediated synaptic responses [29].
• Adenosine, at concentrations ranging from 5 to 100 microM, decreases the efficacy of transmission at the perforant path synapses on dentate granule cells [30].
• Induction of hippocampal seizure activity by perforant path stimulation resulted in an increase in SGZ mitotic activity similar to that seen with pilocarpine administration [31].
• After chronic TMS, FFA was ineffective in enhancing reactivity to perforant path stimulation, probably because it lost the ability to release serotonin [32].

Gene context of Perforant Pathway

• Within resistant sectors, the distribution of immunoreactive elements was comparable in both case groups yet the intensity of immunolabeling was markedly increased in AD cases, particularly in the molecular layer of the dentate gyrus and in the stratum lucidum of CA3 (i.e., the termination zones of perforant pathway and mossy fibers) [33].
• Thus, neprilysin was decreased selectively at the terminal zones and on axons of the lateral perforant path and the mossy fibers [34].
• Perforant pathway stimulation for 24 hours, which evoked population spikes and epileptiform discharges in both dentate granule cells and hippocampal pyramidal neurons, induced GAD65-, GAD67-, and GABA-LI only in granule cells [35].
• These values probably reflect enhanced synthesis since the largest increases were seen in subregions (dentate gyrus, hilus/CA4, CA3) that contain perforant path terminals, and where previously observed intrinsic hippocampal thyrotropin-releasing hormone messenger RNA increases were seen [36].
• Furthermore, although brief high-frequency stimulation of the perforant path produced robust long-term potentiation (LTP) of synaptic responses in the dentate gyrus of +/+ mice, LTP was attenuated in Cm /+ mice [37].

Analytical, diagnostic and therapeutic context of Perforant Pathway

• In the present study, we used quantitative autoradiography to examine the binding properties of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and N-methyl-D-aspartate subclasses of glutamate receptors in frozen brain sections obtained from rats in which perforant-path LTP was induced in vivo [38].
• To investigate cellular mechanisms underlying NMDA receptor plasticity in response to such extensive synaptic reorganization, we quantitatively evaluated changes in intensity levels of NMDAR1 immunofluorescence and NMDAR1 mRNA hybridization within subcellular compartments of dentate gyrus granule cells 2, 5, and 9 d after perforant path lesions [39].
• We have overcome many of the problems of these studies by using an animal model in which epileptic afterdischarges are induced by stimulation of the perforant path, and glutamate and ascorbate are measured using a newly developed microdialysis electrode that combines the advantages of microdialysis and in vivo electrochemistry [40].
• The total PKC concentration did not change for isozymes alpha, beta I, and gamma, but PKC (beta II) concentration increased by 48% following perforant path lesions as detected by Western blot analysis [41].
• METHODS: Male Sprague-Dawley rats had electrodes implanted into the perforant path and dentate granule cell layer under halothane anaesthesia (1-2% in oxygen) [42].

References