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Kindling
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
Although evidence for some form of morphological change or lesion resulting from kindling had been sought from the very outset,2,3 none had been found until publication of two reports involving the hippocampus.77,78 Sutula et al., using a histochemical method, reported that synchronous perforant path stimulation and kindling induce axonal growth and synaptic reorganization in the dentate gyrus and these effects occurred without overt morphological changes.78 Geinisman et al. reported that perforant path stimulation and kindling differentially affected the axospinous synaptic contacts in the middle layer of the dentate gyrus, leading to a selective loss of “nonperforated” synaptic contacts in kindled animals,77 and selective enlargement of active zones in perforated axospinous synapses.79 These phenomena appear to be specific to kindling rather than a consequence of generalized seizure phenomena.80 These reports have relied on methods previously unavailable and provide important new tools for further neuroanatomic research on kindling.
Experimental Models of Status Epilepticus
Published in Steven L. Peterson, Timothy E. Albertson, Neuropharmacology Methods in Epilepsy Research, 2019
Perforant path stimulation results in a limited lesion in the dorsal hippocampus. The model is well suited for studies that examine mechanisms of seizure-induced cell death, seizure-induced changes in hippocampal circuitry, and changes in gene expression. Some limitations of this model are that these seizures do not lead to significant synaptic reorganization or spontaneous seizures which are common in human epilepsy. The model is labor intensive in that the level of anesthesia requires long-term monitoring. However, it takes less than an hour to anesthetize the animal, perform the surgery, and begin the stimulation. The model as originally developed is not well suited for anticonvulsant testing due to the continued presence of the anesthetic urethane. It is not clear whether 1 h of perforant path stimulation in an awake animal used to test the efficacy of anticonvulsants is equivalent to 24 h of stimulation in a urethane-anesthetized animal.
Neurophysiology of Old Neurons and Synapses
Published in David R. Riddle, Brain Aging, 2007
There are three possible mechanisms for decreased synaptic strength: (1) loss of synaptic contacts, (2) decreased transmitter release, and (3) reduced postsynaptic responsiveness to transmitter. Electrophysiological recordings in the dentate gyrus demonstrate a decrease in the fiber potential, a measure of the number of axons activated [86, 97–99]. In addition, a loss of afferent input is supported by anatomical evidence of a diminished number of perforant path synapses and reduced expression of presynaptic biochemical markers, synaptophysin and GAP-43 [100–105]. The idea that aging is associated with a decrease in perforant path input has been challenged by others, however, who have not observed evidence for an age-related decline in synaptic contacts [106–108], even in the face of a loss of afferent input [109]. The discrepancy may be due, in part, to compensatory changes related to sprouting of surviving afferents and enlargement of remaining synapses. In fact, the ratio of the synaptic response to the fiber potential amplitude is increased in aged animals, suggesting that the loss of perforant path input may be compensated for by an increase in the strength of surviving synaptic contacts [86]. Thus, confronted with age-related deafferentation of perforant path afferents, synaptic plasticity processes may preserve transmission and hippocampal memory function, while memory deficits may be observed in animals in which this synaptic plasticity is deficient [3, 110].
Brain Environment Interactions: Stress, Posttraumatic Stress Disorder, and the Need for a Postmortem Brain Collection
Published in Psychiatry, 2022
Elizabeth Osuch, Robert Ursano, He Li, Maree Webster, Chris Hough, Carol Fullerton, Gregory Leskin
Emotional memories can also be modulated by adrenal stress hormones, including epinephrine and glucocorticoids (Quirarte, Roozendaal, and McGaugh, 1997; Roozendaal, Quirarte, and McGaugh, 1997). Epinephrine enhances emotional memory through activation of ® adrenergic receptors (Introini–Collison et al., 1992). Recently, several studies in humans have also indicated that activation of ®- adrenergic receptors can influence long–term declarative memory formation for emotionally arousing events (Cahill et al., 1994; Nielson and Jensen, 1994). This is thought to be part of why memories of emotionally laden events are so much more vivid and long–lasting than memories of neutral events. In the hippocampus propranolol, a ®-receptor antagonist, is capable of blocking activity–dependent long–term potentiation induction of both lateral and medial perforant path–evoked field excitatory postsynaptic potentials (Bramham, Bacher–Svendsen, and Sarvey, 1997). In synaptic transmission between basolateral amygada and ventral endopyriform nucleus, activation of ®-adrenergic receptors by isoproterenol also causes an increase of intracellular c–AMP, and induces a long–term enhancement of excitatory postsynaptic potentials (Huang, Hsu, and Gean, 1996). These findings can facilitate the development of preventive interventions following exposure to traumatic events.
Progesterone treatment in rats after severe global cerebral ischemia promotes hippocampal dentate gyrus neurogenesis and functional recovery
Published in Neurological Research, 2019
Pedro Montes, Rosa María Vigueras-Villaseñor, Julio César Rojas-Castañeda, Tomas Monfil, Miguel Cervantes, Gabriela Moralí
There is evidence that new mature granular neurons are integrated into the trisynaptic hippocampal circuit, since their dendritic spines receive afferents and establish synapses with the perforant path, and their axons are projected to the CA3 subfield, suggesting that they are functional [44,45]. Furthermore, neurogenesis of hippocampal DG has been shown to be associated with the execution of spatial learning tasks of rodents [39,50,51], in conjunction with the hippocampal CA1 region which has been widely related to the spatial learning and memory [50,52]. Cognitive performance of ischemic P4-treated rats having a scant CA1 hippocampal neuronal preservation may represent the result of a cooperative interaction of several mechanisms of plasticity promoted in different neuronal substrates, including the DG, by this neuroactive steroid [27–30,53].
Emerging drugs for focal epilepsy
Published in Expert Opinion on Emerging Drugs, 2018
Galanin was first identified more than 30 years ago as a neuropeptide acting primarily as a modulator of neurotransmission in the brain and the peripheral nervous system but over time it became evident that galanin and other galanin family peptides have a number of additional non-neuronal actions such as on glia, endocrine cells, energy homeostasis and paracrine effects on bones [31]. A number of studies in animal models of epilepsy have shown that galanin is implicated in epilepsy. In the self-sustaining status epilepticus (SSE) model, hippocampal areas are galanin depleted after stimulation of the perforant path dentate gyrus pathway [32] and the duration of the SSE can be markedly shortened by injection of galanin into the dentate hilus [31–33]. The anticonvulsant effect of galanin seems to be mediated by GalR1 and GalR2 receptors but the use of Galanin itself has been limited by poor metabolic stability and lack of blood-brain penetration [31]. Among different potential galanin receptor agonists, those acting on GalR1 receptors have been rapidly excluded as GalR1 receptors also inhibit the release of insulin leading to poor tolerability and many systemic effects [20,31]. GalR2 receptors seem to be localized just on the CNS and, interestingly, their stimulation seem to reduce glutamate release [34], further suggesting a promising anti-seizure activity for this class of compounds.