Impact of Chronic BDNF Depletion on GABAergic Synaptic Transmission in the Lateral Amygdala

Brain-derived neurotrophic factor (BDNF) has previously been shown to play an important role in glutamatergic synaptic plasticity in the amygdala, correlating with cued fear learning. While glutamatergic neurotransmission is facilitated by BDNF signaling in the amygdala, its mechanism of action at inhibitory synapses in this nucleus is far less understood. We therefore analyzed the impact of chronic BDNF depletion on GABAA-mediated synaptic transmission in BDNF heterozygous knockout mice (BDNF+/−). Analysis of miniature and evoked inhibitory postsynaptic currents (IPSCs) in the lateral amygdala (LA) revealed neither pre- nor postsynaptic differences in BDNF+/− mice compared to wild-type littermates. In addition, long-term potentiation (LTP) of IPSCs was similar in both genotypes. In contrast, facilitation of spontaneous IPSCs (sIPSCs) by norepinephrine (NE) was significantly reduced in BDNF+/− mice. These results argue against a generally impaired efficacy and plasticity at GABAergic synapses due to a chronic BDNF deficit. Importantly, the increase in GABAergic tone mediated by NE is reduced in BDNF+/− mice. As release of NE is elevated during aversive behavioral states in the amygdala, effects of a chronic BDNF deficit on GABAergic inhibition may become evident in response to states of high arousal, leading to amygdala hyper-excitability and impaired amygdala function.

Download Full-text

Early low-level developmental arsenic exposure impacts mouse hippocampal synaptic function

10.1101/2021.04.15.440033 ◽

2021 ◽

Author(s):

Karl F Foley ◽

Daniel Barnett ◽

Deborah A Cory-Slechta ◽

Houhui Xia

Keyword(s):

Synaptic Transmission ◽

Hippocampal Slices ◽

Arsenic Exposure ◽

Long Term Potentiation ◽

Epidemiological Studies ◽

Synaptic Function ◽

Learning Deficits ◽

Term Potentiation ◽

The Impact

Background: Arsenic is a well-established carcinogen known to increase all-cause mortality, but its effects on the central nervous system are less well understood. Recent epidemiological studies suggest that early life exposure to arsenic is associated with learning deficits and behavioral changes, and increased arsenic exposure continues to affect an estimated 200 million individuals worldwide. Previous studies on arsenic exposure and synaptic function have demonstrated a decrease in synaptic transmission and long-term potentiation in adult rodents, but have relied on in vitro or extended exposure in adulthood. Therefore, little is known about the effect of arsenic exposure in development. Objective: Here, we studied the effects of gestational and early developmental arsenic exposure in juvenile mice. Specifically, our objective was to investigate the impact of arsenic exposure on synaptic transmission and plasticity in the hippocampus. Methods: C57BL/6 females were exposed to arsenic (0, 50ppb, 36ppm) in their drinking water two weeks prior to mating and continued to be exposed to arsenic throughout gestation and after parturition. We then performed field recordings in acute hippocampal slices from the juvenile offspring prior to weaning (P17-P23). In this paradigm, the juvenile mice are only exposed to arsenic in utero and via the mothers milk. Results: High (36ppm) and relatively low (50ppb) arsenic exposure both lead to decreased basal synaptic transmission in the hippocampus of juvenile mice. There was a mild decrease in paired-pulse facilitation in juvenile mice exposed to high, but not low, arsenic, suggesting the alterations in synaptic transmission are primarily post-synaptic. Finally, high developmental arsenic exposure led to a significant increase in long-term potentiation. Discussion: These results suggest that indirect, ecologically-relevant arsenic exposure in early development impacts hippocampal synaptic transmission and plasticity that could underlie learning deficits reported in epidemiological studies.

Download Full-text

The Kinase Function of MSK1 Regulates BDNF Signaling to CREB and Basal Synaptic Transmission, But Is Not Required for Hippocampal Long-Term Potentiation or Spatial Memory

eNeuro ◽

10.1523/eneuro.0212-16.2017 ◽

2017 ◽

Vol 4 (1) ◽

pp. ENEURO.0212-16.2017 ◽

Cited By ~ 10

Author(s):

Stephanie Daumas ◽

Christopher J. Hunter ◽

Rajen B. Mistry ◽

Lorenzo Morè ◽

Lucia Privitera ◽

...

Keyword(s):

Synaptic Transmission ◽

Spatial Memory ◽

Long Term Potentiation ◽

Term Potentiation ◽

Bdnf Signaling ◽

Basal Synaptic Transmission

Download Full-text

Persistent Synaptic Activity Produces Long-Lasting Enhancement of Endocannabinoid Modulation and Alters Long-Term Synaptic Plasticity

Journal of Neurophysiology ◽

10.1152/jn.01228.2006 ◽

2007 ◽

Vol 97 (6) ◽

pp. 4386-4389 ◽

Cited By ~ 41

Author(s):

Ping Jun Zhu ◽

David M. Lovinger

Keyword(s):

Low Frequency ◽

Long Term Potentiation ◽

Information Storage ◽

Synaptic Activity ◽

Inhibitory Synapses ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Gabaergic Synapses ◽

Activity Dependent

Learning and memory are thought to involve activity-dependent changes in synaptic efficacy such as long-term potentiation (LTP) and long-term depression (LTD). Recent studies have indicated that endocannabinoid-dependent modulation of inhibitory transmission facilitates induction of hippocampal LTP and that endocannabinoids play a key role in certain forms of LTD. Here, we show that repetitive low-frequency synaptic stimulation (LFS) produces persistent up-regulation of endocannabinoid signaling at hippocampal CA1 GABAergic synapses. This LFS also produces LTD of inhibitory synapses and facilitates LTP at excitatory, glutamatergic synapses. These endocannabinoid-mediated plastic changes could contribute to information storage within the brain.

Download Full-text

Involvement of Cerebellum in Emotional Behavior

Physiological Research ◽

10.33549/physiolres.932169 ◽

2011 ◽

pp. S39-S48 ◽

Cited By ~ 11

Author(s):

P. STRATA ◽

B. SCELFO ◽

B. SACCHETTI

Keyword(s):

Long Term Potentiation ◽

Fear Memory ◽

Emotional Behavior ◽

Fear Learning ◽

Inhibitory Synapses ◽

Reversible Inactivation ◽

Sensory Stimuli ◽

Term Potentiation ◽

Reported Data

In the last decade a growing body of data revealed that the cerebellum is involved in the regulation of the affective reactions as well as in forming the association between sensory stimuli and their emotional values. In humans, cerebellar areas around the vermis are activated during mental recall of emotional personal episodes and during learning of a CS-US association. Lesions of the cerebellar vermis may affect retention of a fear memory without altering baseline motor/autonomic responses to the frightening stimuli in both human and animal models. Reversible inactivation of the vermis during the consolidation period impairs retention of fear memory in rodents. Recent findings demonstrate that long-term potentiation (LTP) of synapses in the cerebellar cortex occurs in relation to associative fear learning similar to previously reported data in the hippocampus and amygdala. Plastic changes affect both excitatory and inhibitory synapses. This concomitant potentiation allows the cerebellar cortical network to detect coincident inputs, presumably conveying sensorial stimuli, with better efficacy by keeping the time resolution of the system unchanged. Collectively, these data suggest that the vermis participates in forming new CS-US association and translate an emotional state elaborated elsewhere into autonomic and motor responses.

Download Full-text

Deletion of ErbB4 Disrupts Synaptic Transmission and Long-Term Potentiation of Thalamic Input to Amygdalar Medial Paracapsular Intercalated Cells

Frontiers in Synaptic Neuroscience ◽

10.3389/fnsyn.2021.697110 ◽

2021 ◽

Vol 13 ◽

Author(s):

Douglas Asede ◽

James Okoh ◽

Sabah Ali ◽

Divyesh Doddapaneni ◽

M. McLean Bolton

Keyword(s):

Synaptic Transmission ◽

Critical Role ◽

Inhibitory Neuron ◽

Long Term Potentiation ◽

Learning Mechanisms ◽

Disease Etiology ◽

Term Potentiation ◽

And Function ◽

The Impact

Identification of candidate risk genes and alteration in the expression of proteins involved in regulating inhibitory neuron function in various psychiatric disorders, support the notion that GABAergic neuron dysfunction plays an important role in disease etiology. Genetic variations in neuregulin and its receptor kinase ErbB4, expressed exclusively by GABAergic neurons in the CNS, have been linked with schizophrenia. In the amygdala, ErbB4 is highly expressed in GABAergic intercalated cell clusters (ITCs), which play a critical role in amygdala-dependent behaviors. It is however unknown whether ErbB4 deletion from ITCs affects their synaptic properties and function in amygdala circuitry. Here, we examined the impact of ErbB4 deletion on inhibitory and excitatory circuits recruiting medial paracapsular ITCs (mpITCs) using electrophysiological techniques. Ablation of ErbB4 in mpITCs suppressed NMDA receptor-mediated synaptic transmission at thalamo-mpITC synapses and enhanced thalamic driven GABAergic transmission onto mpITCs. Furthermore, long-term potentiation (LTP) at thalamo-mpITC synapses was compromised in ErbB4 mutant mice, indicating that ErbB4 activity is critical for LTP at these synapses. Together, our findings suggest that ErbB4 deletion from mpITCs disrupts excitation-inhibition balance and learning mechanisms in amygdala circuits.

Download Full-text

The impact of postsynaptic calcium on synaptic transmission — its role in long-term potentiation

Trends in Neurosciences ◽

10.1016/0166-2236(89)90094-5 ◽

1989 ◽

Vol 12 (11) ◽

pp. 444-450 ◽

Cited By ~ 169

Author(s):

R.C. Malenka ◽

J.A. Kauer ◽

D.J. Perkel ◽

R.A. Nicoll

Keyword(s):

Synaptic Transmission ◽

Long Term Potentiation ◽

Term Potentiation ◽

Postsynaptic Calcium ◽

The Impact

Download Full-text

Oxytocin increases inhibitory synaptic transmission and blocks development of long-term potentiation in the lateral amygdala

Journal of Neurophysiology ◽

10.1152/jn.00571.2019 ◽

2020 ◽

Vol 123 (2) ◽

pp. 587-599 ◽

Cited By ~ 2

Author(s):

J. W. Crane ◽

N. M. Holmes ◽

J. Fam ◽

R. F. Westbrook ◽

A. J. Delaney

Keyword(s):

Synaptic Plasticity ◽

Synaptic Transmission ◽

Basolateral Amygdala ◽

Conditioned Fear ◽

Long Term Potentiation ◽

Receptor Activation ◽

Lateral Amygdala ◽

Term Potentiation ◽

Cortical Inputs

Oxytocin (OT) is a neuroactive peptide that influences the processing of fearful stimuli in the amygdala. In the central nucleus of the amygdala, the activation of OT receptors alters neural activity and ultimately suppresses the behavioral response to a fear conditioned stimulus. Receptors for OT are also found in the lateral amygdala (LA), and infusion of OT into the basolateral amygdala complex affects the formation and consolidation of fear memories. Yet, how OT receptor activation alters neurons and neural networks in the LA is unknown. In this study we used whole cell electrophysiological recordings to determine how OT-receptor activation changes synaptic transmission and synaptic plasticity in the LA of Sprague-Dawley rats. Our results demonstrate that OT-receptor activation results in a 200% increase in spontaneous inhibitory transmission in the LA that leads to the activation of presynaptic GABAB receptors. The activation of these receptors inhibits excitatory transmission in the LA, blocking long-term potentiation of cortical inputs onto LA neurons. Hence, this study provides the first demonstration that OT influences synaptic transmission and plasticity in the LA, revealing a mechanism that could explain how OT regulates the formation and consolidation of conditioned fear memories in the amygdala. NEW & NOTEWORTHY This study investigates modulation of synaptic transmission by oxytocin (OT) in the lateral amygdala (LA). We demonstrate that OT induces transient increases in spontaneous GABAergic transmission by activating interneurons in the basolateral amygdala. The resultant increase in GABA release in the LA activates presynaptic GABAB receptors on both inhibitory and excitatory inputs onto LA neurons, reducing release probability at these synapses. We subsequently demonstrate that OT modulates synaptic plasticity at cortical inputs to the LA.

Download Full-text