Zinc May Play Prominent Role in Fear Response and Other Learned Behavior, McLean Hospital Researchers Find

September 28, 2006

Public Affairs
Cindy Lepore

Belmont, MA - The metal zinc released in the brain's amygdala region has been linked to the ability to generate the learned fear response, researchers at Harvard-affiliated McLean Hospital are reporting. The finding could help in understanding more about zinc intake, its importance in the daily diet and its role in memory.

In a paper (PubMed) published in the early online issue of the Proceedings of the National Academy of Sciences (Oct. 10 print date), the researchers reported that ionic zinc, which is co-released with the neurotransmitter glutamate at synapses or contact points between neurons in the amygdala, serves an essential function in modifying the activity of those contact points, increasing the transmission of electrical signals and boosting the activity of neurons involved in fear conditioning.

"This is truly the first study providing a mechanistic explanation for the role of zinc in the central nervous system," said Vadim Bolshakov, PhD, lead researcher, director of the Cellular Neurobiology Laboratory at McLean Hospital and associate professor of psychiatry at Harvard Medical School. Previous studies had shown that the amygdala, a brain structure important for emotional responses, is the place where fear memory is formed.

The functional role of zinc in the central nervous system has, until now, been unknown.

In this study, the researchers have shown that zinc is enriched in sections of the amygdala as well as the auditory cortex, an area of the brain which conveys information important for learning fear in response to sounds.

To explore the role of zinc in neuronal circuits involved in fear behavior, the researchers recorded electrical activity of neurons in amygdala slices taken from rats' brains.

"Our results provide the first direct evidence that zinc released during the communication between neurons has an impact on neurotransmission in the amygdala, thus potentially contributing to fear learning," Bolshakov said.

This occurs when zinc-releasing cells, also secreting the neurotransmitter glutamate, overpower other cells releasing the inhibitory neurotransmitter GABA. As a result, neurons in the amygdala become more excitable, thus contributing to the fear response. The blocking of inhibition in the amygdala by zinc released during the transmission of signals makes the brain more susceptible to forming long-term changes, including lasting memory for fear, according to Bolshakov.

"This novel regulatory mechanism may serve an essential control function in assuring… long-lasting. . . modifications in the neural circuit of a learned behavior," the paper says.

According to Wikipedia, zinc is found in oysters and, to a far lesser degree, in most animal proteins, beans, nuts, whole grains, pumpkin seeds and sunflower seeds. Eyesight, taste, smell and memory were previously connected with zinc and a deficiency in zinc can cause disruption of these functions.

The McLean study is a collaborative effort with 2000 Nobel Prize recipient Eric Kandel at Columbia University and Gleb Shumyatsky of Rutgers. Other researchers who participated in the study are Sodikdjon Kodirov, PhD, Shuichi Takizawa, PhD, and Jamie Joseph.

The researchers have for some time been studying how changes in the brain may affect learning and memory. In earlier animal studies, they were able to measure changes in the brain and correlate them with changes in behavior associated with learning. In a paper published last year, they reported that the protein stathmin, expressed in the amygdala region, is also linked to the ability to produce the fear response-both the expression of innate fear and the formation of memory for learned fear. They found that mice which were genetically modified not to produce stathmin showed deficits in neural transmission and exhibited decreased memory in fear conditioning and the failure to recognize danger in innately aversive environments.

McLean Hospital is an affiliate of Harvard Medical School, an affiliate of Massachusetts General Hospital and a member of Partners HealthCare.

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