Hippocampal theta, gamma, and theta-gamma coupling: effects of aging, environmental change, and cholinergic activation

Abstract

Hippocampal theta and gamma oscillations coordinate the timing of multiple inputs to hippocampal neurons and have been linked to information processing and the dynamics of encoding and retrieval. One major influence on hippocampal rhythmicity is from cholinergic afferents. In both humans and rodents, aging is linked to impairments in hippocampus-dependent function along with degradation of cholinergic function. Cholinomimetics can reverse some age-related memory impairments and modulate oscillations in the hippocampus. Therefore, one would expect corresponding changes in these oscillations and possible rescue with the cholinomimetic physostigmine. Hippocampal activity was recorded while animals explored a familiar or a novel maze configuration. Reexposure to a familiar situation resulted in minimal aging effects or changes in theta or gamma oscillations. In contrast, exploration of a novel maze configuration increased theta power; this was greater in adult than old animals, although the deficit was reversed with physostigmine. In contrast to the theta results, the effects of novelty, age, and/or physostigmine on gamma were relatively weak. Unrelated to the behavioral situation were an age-related decrease in the degree of theta-gamma coupling and the fact that physostigmine lowered the frequency of theta in both adult and old animals. The results indicate that age-related changes in gamma and theta modulation of gamma, while reflecting aging changes in hippocampal circuitry, seem less related to aging changes in information processing. In contrast, the data support a role for theta and the cholinergic system in encoding and that hippocampal aging is related to impaired encoding of new information.

GABAergic Networks in the Prefrontal Cortex and Working Memory

“…In humans and primates, the total number of prefrontal cortex cells is preserved in aging (Peters et al, 1996). There is, however, evidence of significant age-related changes in neuronal morphology, including apical dendritic regression, loss of synapses, and a decrease in spine number (Peters et al, 1996;Bloss et al, 2013). Moreover, inhibitory circuits in the prefrontal cortex are vulnerable to age-related changes that may underlie cognitive decline at advanced age.…”

“…Moreover, inhibitory circuits in the prefrontal cortex are vulnerable to age-related changes that may underlie cognitive decline at advanced age. These changes include increased expression of GAD, the critical enzyme for GABA synthesis, altered expression of GABA B receptors, and reduced expression of GAT-1, the GABA transporter responsible for the reuptake of GABA at the synapse, in aged prefrontal cortex compared with young (Bañuelos et al, 2014). In contrast to Yoon et al (2016), increased inhibition in the prefrontal cortex negatively affects working memory performance in aged rats, implying that the relationship between GABAergic drive and cognitive performance differs in an age-dependent manner.…”

“…An emerging literature demonstrates that, in aging, significant changes in both excitatory and inhibitory synaptic transmission may be related to cognitive impairment (Bories et al, 2013). Theta (4 -8 Hz) and gamma (20 -100 Hz) oscillations, neural oscillations that have been linked to information processing and cognition, are attenuated in certain behavioral conditions in aging (Jacobson et al, 2013).…”

“…This type of memory critically depends on the prefrontal cortex, as first described based on neurophysiological and lesion studies in monkeys (Fuster, 1990;Goldman-Rakic, 1990). The ability to maintain information in prefrontal cortex after the sensory stimulus is removed is linked to persistent firing of excitatory glutamatergic pyramidal cells (Goldman-Rakic, 1996), but disruption of GABAergic circuits in the prefrontal cortex can produce profound impairments in working memory (Enomoto et al, 2011). Conversely, pharmacologically targeting this local inhibitory circuitry can reverse age-related working memory deficits (Bañuelos et al, 2014).…”

“…The ability to maintain information in prefrontal cortex after the sensory stimulus is removed is linked to persistent firing of excitatory glutamatergic pyramidal cells (Goldman-Rakic, 1996), but disruption of GABAergic circuits in the prefrontal cortex can produce profound impairments in working memory (Enomoto et al, 2011). Conversely, pharmacologically targeting this local inhibitory circuitry can reverse age-related working memory deficits (Bañuelos et al, 2014). These results from animal studies suggest a critical role for inhibitory GABAergic circuits in prefrontal cortex-dependent working memory (Murray et al, 2015).…”