Neurophysiological and behavioral measures were obtained from 32 senescent (28--34 mo) and 32 mature adult (10--16 mo) rats. Extracellularly recorded synaptic responses were obtained from electrodes chronically implanted in the fascia dentata and perforant path. The rats were first tested on a circular platform, which favored the use of spatial cues for its solution, and the senescent rats were shown to exhibit poorer memory for the rewarded place. When granule cell synaptic responses were recorded after a single session of very brief high-frequency stimulation, the amount of elevation and time course of decline were equivalent between age groups. Af ter three repetitions, however, the young rats maintained the increased synaptic strength for at least 14 days, whereas the old rats declined after the first session. The amount of synaptic enhancement was statistically correlated with the ability to perform the circular platform task both within and between groups. Furthermore, the aftereffects of the high-frequency stimulation selectively impaired the old rats' spontaneous alternation behavior on a T-maze. Certain other neurophysiological and electroencephalographic measures did not distinguish between age groups. The results are discussed in terms of the synaptic theory of memory formation and of their relevance to the aging process.

Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat.

Many potential treatments for Alzheimer9s disease target amyloid-β peptides (Aβ), which are widely presumed to cause the disease. The microtubule-associated protein tau is also involved in the disease, but it is unclear whether treatments aimed at tau could block Aβ-induced cognitive impairments. Here, we found that reducing endogenous tau levels prevented behavioral deficits in transgenic mice expressing human amyloid precursor protein, without altering their high Aβ levels. Tau reduction also protected both transgenic and nontransgenic mice against excitotoxicity. Thus, tau reduction can block Aβ- and excitotoxin-induced neuronal dysfunction and may represent an effective strategy for treating Alzheimer9s disease and related conditions.

https://science.sciencemag.org/content/sci/316/5825/750.full.pdf

Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model

Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region

Recent studies have revealed that mossy fiber axons of granule cells in the dentate gyrus undergo reorganization of their terminal projections in both animal models of epilepsy and human epilepsy This synaptic reorganization has been demonstrated by the Timm method, a histochemical technique that selectively labels synaptic terminals of mossy fibers because of their high zinc content It has been generally presumed that the reorganization of the terminal projections of the mossy fiber pathway is a consequence of axonal sprouting and synaptogenesis by mossy fibers To evaluate this possibility further, the time course for development of Timm granules, which correspond ultrastructurally to mossy fiber synaptic terminals, was examined in the supragranular layer of the dentate gyrus at the initiation of kindling stimulation with an improved scoring method for assessment of alterations in Timm histochemistry 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 Mossy fiber synaptic terminals developed in the supragranular region of the dentate gyrus by 4 d after initiation of kindling stimulation in a time course compatible with axon sprouting The induced alterations in the terminal projections of the mossy fiber pathway progressed with the evolution of behavioral kindled seizures, became permanent in parallel with the development of longlasting susceptibility to evoked seizures, and were observed as long as 8 months after the last evoked kindled seizure The results demonstrated a strong correlation between mossy fiber synaptic reorganization and the development, progression, and permanence of the kindling phenomenon

https://www.jneurosci.org/content/jneuro/11/9/2795.full.pdf

Mossy fiber synaptic reorganization induced by kindling: Time course of development, progression, and permanence

Two markers of neuronal plasticity were used to compare the response of the human central nervous system to neuronal loss resulting from Alzheimer's disease with the response of rats to a similar neuronal loss induced by lesions. In rats that had received lesions of the entorhinal cortex, axon sprouting of commissural and associational fibers into the denervated molecular layer of the dentate gyrus was paralleled by a spread in the distribution of tritiated kainic acid-binding sites. A similar expansion of kainic acid receptor distribution was observed in hippocampal samples obtained postmortem from patients with Alzheimer's disease. An enhancement of acetylcholinesterase activity in the dentate gyrus molecular layer, indicative of septal afferent sprouting, was also observed in those patients with a minimal loss of cholinergic neurons. These results are evidence that the central nervous system is capable of a plastic response in Alzheimer's disease. Adaptive growth responses occur along with the degenerative events.

http://science.sciencemag.org/content/sci/230/4730/1179.full.pdf

Plasticity of hippocampal circuitry in Alzheimer's disease

Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: Recovery of alternation performance following unilateral entorhinal cortex lesions

Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: open field activity and cue utilization following bilateral entorhinal cortex lesions.

Quantitative autoradiographic analysis of the time course of proliferation of contralateral entorhinal efferents in the dentate gyrus denervated by ipsilateral entorhinal lesions

Jacquelyn Loesche

Papers

Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: Recovery of alternation performance following unilateral entorhinal cortex lesions

Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: open field activity and cue utilization following bilateral entorhinal cortex lesions.

Quantitative autoradiographic analysis of the time course of proliferation of contralateral entorhinal efferents in the dentate gyrus denervated by ipsilateral entorhinal lesions