Interneurons of the hippocampus

Early clinical observations and recent systematic studies overwhelmingly document a greater role for psychosocial stressors in association with the first episode of major affective disorder than with subsequent episodes. The author postulates that both sensitization to stressors and episode sensitization occur and become encoded at the level of gene expression. In particular, stressors and the biochemical concomitants of the episodes themselves can induce the protooncogene c-fos and related transcription factors, which then affect the expression of transmitters, receptors, and neuropeptides that alter responsivity in a long-lasting fashion. Thus, both stressors and episodes may leave residual traces and vulnerabilities to further occurrences of affective illness. These data and concepts suggest that the biochemical and anatomical substrates underlying the affective disorders evolve over time as a function of recurrences, as does pharmacological responsivity. This formulation highlights the critical importance of early intervention in the illness in order to prevent malignant transformation to rapid cycling, spontaneous episodes, and refractoriness to drug treatment.

Transduction of psychosocial stress into the neurobiology of recurrent affective disorder.

Synaptic plasticity in adult neural circuits may involve the strengthening or weakening of existing synapses as well as structural plasticity, including synapse formation and elimination. Indeed, long-term in vivo imaging studies are beginning to reveal the structural dynamics of neocortical neurons in the normal and injured adult brain. Although the overall cell-specific morphology of axons and dendrites, as well as of a subpopulation of small synaptic structures, are remarkably stable, there is increasing evidence that experience-dependent plasticity of specific circuits in the somatosensory and visual cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively. This Review focuses on recent evidence for such structural forms of synaptic plasticity in the mammalian cortex and outlines open questions.

Experience-dependent structural synaptic plasticity in the mammalian brain.

Chronic stress produces structural changes and neuronal damage especially in the hippocampus. Because neurotrophic factors affect neuron survival, we questioned whether they might be relevant to the heightened vulnerability of hippocampal neurons following stress. To begin investigating this possibility, we examined the effects of immobilization stress (2 hr/d) on the expression of neurotrophic factors in rat brains using in situ hybridization. We found that single or repeated immobilization markedly reduced brain-derived neurotrophic factor (BDNF) mRNA levels in the dentate gyrus and hippocampus. In contrast, NT-3 mRNA levels were increased in the dentate gyrus and hippocampus in response to repeated but not acute stress. Stress did not affect the expression of neurotrophin-4, or tyrosine receptor kinases (trkB or C). Corticosterone negative feedback may have contributed in part to the stress-induced decreases in BDNF mRNA levels, but stress still decreased BDNF in the dentate gyrus in adrenalectomized rats suggesting that additional components of the stress response must also contribute to the observed changes in BDNF. However, corticosterone-mediated increases in NT-3 mRNA expression appeared to be primarily responsible for the effects of stress on NT-3. These findings demonstrate that BDNF and NT-3 are stress-responsive genes and raise the possibility that alterations in the expression of these or other growth factors might be important in producing some of the physiological and pathophysiological effects of stress in the hippocampus.

https://www.jneurosci.org/content/jneuro/15/3/1768.full.pdf

Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus

The distribution of the mossy fiber synaptic terminals was examined using the Timm histochemical method in surgically excised hippocampus and dentate gyrus from patients who underwent lobectomy of the anterior part of the temporal lobe for refractory partial complex epilepsy The dentate gyrus of epileptic patients demonstrated intense Timm granules and abundant mossy fiber synaptic terminals in the supragranular region and the inner molecular layer In contrast, the dentate gyrus of presenescent nonepileptic primates demonstrated no Timm granules in the supragranular region In nonepileptic senescent primates, occasional very sparse supragranuler Timm granules were observed that were easily distinguished from the dense pattern observed in association with human epilepsy The results are morphological evidence of mossy fiber synaptic reorganization in the temporal lobe of epileptic humans, and suggest the intriguing possibility that mossy fiber sprouting and synaptic reorganization induced by repeated partial complex seizures may play a role in human epilepsy

Mossy fiber synaptic reorganization in the epileptic human temporal lobe.

Abnormal functional activity induces long-lasting physiological alterations in neural pathways that may play a role in the development of epilepsy. The cellular mechanisms of these alterations are not well understood. One hypothesis is that abnormal activity causes structural reorganization of neural pathways and promotes epileptogenesis. This report provides morphological evidence that synchronous perforant path activation and kindling of limbic pathways induce axonal growth and synaptic reorganization in the hippocampus, in the absence of overt morphological damage. The results show a previously unrecognized anatomic plasticity associated with synchronous activity and development of epileptic seizures in neural pathways.

https://science.sciencemag.org/content/sci/239/4844/1147.full.pdf

Xiao-Xian He

Papers

Synaptic reorganization in the hippocampus induced by abnormal functional activity.