scholarly journals Pre- and Postnatal Propylthiouracil-Induced Hypothyroidism Impairs Synaptic Transmission and Plasticity in Area CA1 of the Neonatal Rat Hippocampus

Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 4195-4203 ◽  
Author(s):  
Li Sui ◽  
M. E. Gilbert
Keyword(s):  
Thyroid Hormone ◽  
Synaptic Transmission ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Learning Deficits ◽  
Paired Pulse ◽  
Area Ca1 ◽  
Term Potentiation ◽  
Paired Pulse Depression

Abstract Thyroid hormones are essential for neonatal brain development. It is well established that insufficiency of thyroid hormone during critical periods of development can impair cognitive functions. The mechanisms that underlie learning deficits in hypothyroid animals, however, are not well understood. As impairments in synaptic function are likely to contribute to cognitive deficits, the current study tested whether thyroid hormone insufficiency during development would alter quantitative characteristics of synaptic function in the hippocampus. Developing rats were exposed in utero and postnatally to 0, 3, or 10 ppm propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, administered in the drinking water of dams from gestation d 6 until postnatal day (PN) 30. Excitatory postsynaptic potentials and population spikes were recorded from the stratum radiatum and the pyramidal cell layer, respectively, in area CA1 of hippocampal slices from offspring between PN21 and PN30. Baseline synaptic transmission was evaluated by comparing input-output relationships between groups. Paired-pulse facilitation, paired-pulse depression, long-term potentiation, and long-term depression were recorded to examine short- and long-term synaptic plasticity. PTU reduced thyroid hormones, reduced body weight gain, and delayed eye-opening in a dose-dependent manner. Excitatory synaptic transmission was increased by developmental exposure to PTU. Thyroid hormone insufficiency was also dose-dependently associated with a reduction paired-pulse facilitation and long-term potentiation of the excitatory postsynaptic potential and elimination of paired-pulse depression of the population spike. The results indicate that thyroid hormone insufficiency compromises the functional integrity of synaptic communication in area CA1 of developing rat hippocampus and suggest that these changes may contribute to learning deficits associated with developmental hypothyroidism.

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

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.

Changes in paired-pulse facilitation correlate with induction of long-term potentiation in area CA1 of rat hippocampal slices

Neuroscience ◽  
1996 ◽  
Vol 76 (3) ◽  
pp. 829-843 ◽  
Author(s):  
A.M Kleschevnikov ◽  
M.V Sokolov ◽  
U Kuhnt ◽  
G.S Dawe ◽  
J.D Stephenson ◽  
...  
Keyword(s):  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Paired Pulse ◽  
Paired Pulse Facilitation ◽  
Area Ca1 ◽  
Term Potentiation

Modulation of synaptic transmission and long-term potentiation: effects on paired pulse facilitation and EPSC variance in the CA1 region of the hippocampus

1993 ◽  
Vol 70 (4) ◽  
pp. 1451-1459 ◽  
Author(s):  
T. Manabe ◽  
D. J. Wyllie ◽  
D. J. Perkel ◽  
R. A. Nicoll
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Similar Amount ◽  
Stimulus Strength ◽  
Paired Pulse ◽  
Paired Pulse Facilitation ◽  
Epsc Amplitude ◽  
Term Potentiation

1. Whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) were made from guinea pig hippocampal CA1 pyramidal cells. The sensitivity of paired pulse facilitation (PPF) and EPSC variance to changes in synaptic transmission was investigated and the results were compared with the changes in these parameters evoked by long-term potentiation (LTP). 2. Presynaptic manipulations, such as activation of presynaptic gamma-aminobutyric acid-B receptors by baclofen, blockade of presynaptic adenosine receptors by theophylline, blockade of presynaptic potassium channels by cesium, and increasing the Ca(2+)-Mg2+ ratio in the external recording solution, each reliably changed PPF in a fashion reciprocal to the change in the EPSC amplitude. However, recruitment of additional synaptic release sites by increasing stimulus strength and antagonism of non-N-methyl-D-aspartate (NMDA) glutamate receptors by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) failed to alter PPF. 3. Presynaptic manipulations including increased stimulus strength gave the predicted changes in the value of mean 2/variance (M2/sigma 2). Moreover, postsynaptic manipulations that altered EPSC amplitude, including blockade of non-NMDA receptors by CNQX, or changing the holding potential of the postsynaptic cell, gave little change in M2/sigma 2, as would be predicted for manipulations resulting in a uniform postsynaptic change. 4. LTP caused no change in PPF, whereas the presynaptic manipulations, which caused a similar amount of potentiation to that induced by LTP, significantly decreased PPF. On the other hand, LTP did increase M2/sigma 2, although the increase was less than that predicted for a purely presynaptic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

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