Can you imagine a drug that would make it easier to learn a language, sharpen your memory and help those with dementia and Alzheimer’s disease by rewiring the brain and keeping neurons alive?
New Rutgers research published in the Journal of Neuroscience found that a drug – RGFP966 – administered to rats made them more attuned to what they were hearing, able to retain and remember more information, and develop new connections that allowed these memories to be transmitted between brain cells.
“Memory-making in neurological conditions like Alzheimer’s disease is often poor or absent altogether once a person is in the advanced stages of the disease,” said Kasia M. Bieszczad, lead author and assistant professor in Behavioral and Systems Neuroscience in the Department of Psychology. “This drug could rescue the ability to make new memories that are rich in detail and content, even in the worst case scenarios.”
What happens with dementias such as Alzheimer’s is that brain cells shrink and die because the synapses that transfer information from one neuron to another are no longer strong and stable. There is no therapeutic treatment available that reverses this situation.
The drug being tested in this animal study is among a class known as HDAC inhibitors – now being used in cancer therapies to stop the activation of genes that turn normal cells into cancerous ones. In the brain, the drug makes the neurons more plastic, better able to make connections and create positive changes that enhance memory. Researchers found that laboratory rats, taught to listen to a certain sound in order to receive a reward, and given the drug after training, remembered what they learned and responded correctly to the tone at a greater rate than those not given the drug.
Scientists also found that the rodents were more “tuned in” to the relevant acoustic signals they heard during their training – an important finding Bieszczad said because setting up the brain to better process and store significant sounds is critical to human speech and language.
“People learning to speak again after a disease or injury as well as those undergoing cochlear implantation to reverse previous deafness, may be helped by this type of therapeutic treatment in the future,” said Bieszczad “The application could even extend to people with delayed language learning abilities or people trying to learn a second language.”
This hypersensitivity in processing auditory information enabled the neurons to reorganize and create new pathways – allowing more of the information they learned to become a long-term memory, said Bieszczad who collaborated with colleagues in the Department of Neurobiology and Behavior at the University of California Irvine.
“People normally remember an experience with limited detail – not everything we see, hear and feel is remembered,” she said. “What has happened here is that memory becomes closer to a snapshot of the actual experience instead of being sparse, limited or inaccurate.”
About this Alzheimer’s disease research
Source: Robin Lally – Rutgers University Image Credit: The image is adapted from the Rutgers University press release Original Research:Abstract for “Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation” by Kasia M. Bieszczad, Kiro Bechay, James R. Rusche, Vincent Jacques, Shashi Kudugunti, Wenyan Miao, Norman M. Weinberger, James L. McGaugh, and Marcelo A. Wood in Journal of Neuroscience. Published online September 23 2015 doi:10.1523/JNEUROSCI.0914-15.2015
Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation
Research over the past decade indicates a novel role for epigenetic mechanisms in memory formation. Of particular interest is chromatin modification by histone deacetylases (HDACs), which, in general, negatively regulate transcription. HDAC deletion or inhibition facilitates transcription during memory consolidation and enhances long-lasting forms of synaptic plasticity and long-term memory. A key open question remains: How does blocking HDAC activity lead to memory enhancements? To address this question, we tested whether a normal function of HDACs is to gate information processing during memory formation. We used a class I HDAC inhibitor, RGFP966 (C21H19FN4O), to test the role of HDAC inhibition for information processing in an auditory memory model of learning-induced cortical plasticity. HDAC inhibition may act beyond memory enhancement per se to instead regulate information in ways that lead to encoding more vivid sensory details into memory. Indeed, we found that RGFP966 controls memory induction for acoustic details of sound-to-reward learning. Rats treated with RGFP966 while learning to associate sound with reward had stronger memory and additional information encoded into memory for highly specific features of sounds associated with reward. Moreover, behavioral effects occurred with unusually specific plasticity in primary auditory cortex (A1). Class I HDAC inhibition appears to engage A1 plasticity that enables additional acoustic features to become encoded in memory. Thus, epigenetic mechanisms act to regulate sensory cortical plasticity, which offers an information processing mechanism for gating what and how much is encoded to produce exceptionally persistent and vivid memories.
SIGNIFICANCE STATEMENT Here we provide evidence of an epigenetic mechanism for information processing. The study reveals that a class I HDAC inhibitor (Malvaez et al., 2013; Rumbaugh et al., 2015; RGFP966, chemical formula C21H19FN4O) alters the formation of auditory memory by enabling more acoustic information to become encoded into memory. Moreover, RGFP966 appears to affect cortical plasticity: the primary auditory cortex reorganized in a manner that was unusually “tuned-in” to the specific sound cues and acoustic features that were related to reward and subsequently remembered. We propose that HDACs control “informational capture” at a systems level for what and how much information is encoded by gating sensory cortical plasticity that underlies the sensory richness of newly formed memories.
“Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation” by Kasia M. Bieszczad, Kiro Bechay, James R. Rusche, Vincent Jacques, Shashi Kudugunti, Wenyan Miao, Norman M. Weinberger, James L. McGaugh, and Marcelo A. Wood in Journal of Neuroscience. Published online September 23 2015 doi:10.1523/JNEUROSCI.0914-15.2015