Summary: A new study shows that balanced neural inhibition in the hippocampus is crucial for recognition memory, the ability to remember objects we’ve recently encountered. Using a rat model, researchers altered GABA-mediated inhibition in either the hippocampus or prefrontal cortex to see how each region contributed to memory.
They found that both too little and too much inhibition in the hippocampus disrupted object recognition, while manipulating inhibition in the prefrontal cortex had no effect. The findings suggest that stable, well-regulated neural activity — not simply more or less of it — is essential for memory function. This work may help guide new treatments for cognitive disorders marked by disrupted inhibition, including dementia and schizophrenia.
Key Facts
- Hippocampal Balance Required: Recognition memory failed when hippocampal inhibition was either too weak or too strong.
- Region-Specific Effect: Altering inhibition in the prefrontal cortex did not impact object recognition performance.
- Clinical Implications: Results highlight neural imbalance, not underactivity, as a key contributor to memory impairment in multiple brain disorders.
Source: University of Nottingham
A new study has revealed that neural inhibition and balanced neural activity in a specific area of the brain is required for recognition memory.
The findings could help provide better understanding of cognitive disorders, including schizophrenia, dementia, and age-related memory impairments.
Scientists from the University of Nottingham’s School of Psychology, in collaboration with colleagues from the University of Manchester, found that neural inhibition within the hippocampus, but not the prefrontal cortex, is important for object recognition memory.
More specifically, both too little and too much neural inhibition in the hippocampus disrupted such memory, suggesting that balanced levels of neural activity in the hippocampus are important for object recognition to function optimally.
The findings have been published today in The Journal of Neuroscience.
Neurons in the brain interact with each other by releasing chemicals, so-called neurotransmitters. Gamma-aminobutyric acid (GABA) is the most common inhibitory neurotransmitter, which is important to restrain neural activity, preventing neurons from getting too trigger-happy and from firing too much or responding to irrelevant stimuli.
In the extreme, impaired inhibitory GABA transmission can cause epileptic seizures. In addition, more subtle impairments in GABA-mediated neural inhibition, especially in the hippocampus and prefrontal cortex, two brain regions implicated in memory and other cognitive functions, have been linked to a range of brain disorders characterised by cognitive impairments, including schizophrenia, age-related cognitive decline and early stages of Alzheimer’s.
Charlie Taylor, now a Research Fellow in the School of Medicine, led the research as part of her PhD project in the School of Psychology. She said: “Impaired GABAergic neural inhibition in the prefrontal cortex and hippocampus has emerged as a key neuropathological feature of cognitive disorders, but we did not know if these brain abnormalities contribute to memory impairment relevant to these conditions.
“Many cognitive disorders show impairments in recognition memory, which is a type of memory that allows people to remember newly encountered objects (e.g. their new bike, a new gadget, a new face, etc.).
“We can test a type of memory related to this in rats using an object recognition test, which is widely used in preclinical models of brain disorders. Using a rat model, we were able to change GABA-mediated neural inhibition specifically in the hippocampus or prefrontal cortex and identify exactly how this affected their recognition of objects.”
The researchers found that both too little and too much neural inhibition in the hippocampus disrupts recognition memory, suggesting that balanced levels of neural inhibition are needed to maintain this type of memory function.
The findings also show that the object recognition test, which is widely used by researchers in academia and drug discovery industry, can be used to study dysfunction of GABA-mediated neural inhibition in the hippocampus (but not prefrontal cortex) in rat models of brain disorders and also to test new treatments targeting such dysfunction.
Dr Tobias Bast, from the School of Psychology supervised the research, he said: “These findings provide further understanding of brain mechanisms underlying cognitive impairments, including problems with memory.
“People often assume that cognitive impairments are caused by decreased activity in certain brain regions, and that ‘boosting’ brain activity may improve brain functions. However, these new findings show that that the opposite can be the case! Faulty neural inhibition, which leads to increased, but poorly controlled, brain activity can cause problems.
“This has important implications for new treatments, suggesting that it is important to re-balance neural activity, for example by drugs or neuromodulation technology, in specific brain regions to restore cognitive functions, such as memory.”
Key Questions Answered:
A: Recognition memory relies on carefully balanced inhibitory signaling in the hippocampus. When inhibition is either reduced or excessive, neural activity becomes unstable, disrupting the brain’s ability to encode and recall newly encountered objects.
A: No. Manipulating GABA-mediated inhibition in the prefrontal cortex had no measurable effect on object recognition, showing that this form of memory depends specifically on hippocampal function.
A: Many disorders involving memory loss also show impaired GABAergic inhibition. This study suggests that restoring balanced inhibition — rather than simply increasing neural activity — may be key to improving memory in conditions like schizophrenia, dementia, and age-related cognitive decline.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience and memory research news
Author: Emma Thorne
Source: University of Nottingham
Contact: Emma Thorne – University of Nottingham
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Too Little and Too Much: Balanced Hippocampal, But Not Medial Prefrontal, Neural Activity Is Required for Intact Novel Object Recognition in Rats” by Charlie Taylor et al. Journal of Neuroscience
Abstract
Too Little and Too Much: Balanced Hippocampal, But Not Medial Prefrontal, Neural Activity Is Required for Intact Novel Object Recognition in Rats
Impaired GABAergic inhibition, so-called neural disinhibition, in the prefrontal cortex and hippocampus has been linked to cognitive deficits. The novel object recognition (NOR) task has been used widely to study cognitive deficits in rodents.
However, the contribution of prefrontal cortical and hippocampal GABAergic inhibition to NOR task performance has not been established.
Here, we investigated NOR task performance in male Lister hooded rats following regional neural disinhibition or functional inhibition, using intracerebral microinfusion of the GABAA receptor antagonist picrotoxin or agonist muscimol, respectively.
Our infusion targets were the medial prefrontal cortex (mPFC), dorsal hippocampus (DH), and ventral hippocampus (VH). Using a within-subject design, we compared NOR task performance (1 min retention delay) following bilateral regional saline, picrotoxin, or muscimol infusions made before the acquisition phase.
In mPFC, neither functional inhibition nor neural disinhibition affected object recognition memory. However, in both the DH and VH, neural disinhibition impaired NOR relative to saline control, mainly by reducing novel object exploration time.
In addition, functional inhibition of the DH impaired NOR, whereas VH functional inhibition tended to reduce novel object exploration at the highest dose used (alongside substantial nonspecific behavioral effects). Overall, our data suggest that hippocampal, but not prefrontal, GABAergic inhibition contributes to NOR at a 1 min retention delay.
Moreover, such NOR performance likely requires balanced neural activity in the DH, with both too little and too much DH activity impairing NOR memory.
Our findings support that the NOR task can be used to investigate hippocampal GABAergic dysfunction in rodent models.
